nanostructure lipid carriers a modish contrivance to overcome the ultraviolet effects

Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx Contents lists available at ScienceDirect Egyptian Journal of Basic and Applied Sciences journal homepage: www.elsevier.com/locate/ejbas Review Article Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Priyanka Jain, Prerna Rahi, Vikas Pandey, Saket Asati, Vandana Soni ⇑ Department of Pharmaceutical Sciences, Dr Hari Singh Gour University, Sagar, Madhya Pradesh 470 003, India a r t i c l e i n f o Article history: Received 28 September 2016 Received in revised form February 2017 Accepted February 2017 Available online xxxx Keywords: UV blocker UV radiation Nanostructured lipid carriers (NLCs) Sun Protection Factor (SPF) a b s t r a c t Protection of the skin from the ultraviolet radiation is the prime concern of society An increase in the adverse effects by ultraviolet (UV) radiation on the skin promoted cosmetic formulators to work in the area of UV blockers and their effective means of delivery Nanostructured lipid carriers (NLCs) is a modern and successful lipid carrier system in the cosmetic world associated with various advantages i.e., stability, effective drug loading capacity etc NLCs also permits to load 70% of UV blockers which are sufficient to obtain recommended Sun Protection Factor (SPF) which makes them suitable delivery systems for topical application of the UV blockers Ó 2017 Production and hosting by Elsevier B.V on behalf of Mansoura University This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Contents Introduction 1.1 Skin and radiation Adverse effects of UV radiations 2.1 Sunburn (erythema) and tanning 2.2 Immune response 2.3 Skin photoaging 2.4 Skin cancer 2.5 Eye diseases Sunscreen agents 3.1 Chemical sunscreens (Organic) 3.2 Physical sunscreens (Inorganic) Novel drug delivery systems and formulations 4.1 Liposomes 4.2 Transfersomes 4.3 Niosomes 4.4 Ethosomes 4.5 Solid lipid nanoparticles (SLNs) Nanostructured lipid carriers (NLCs) 5.1 Imperfect NLCs 5.2 Amorphous NLCs 5.3 Multiple NLCs 5.4 Advantages over other lipid carriers 5.5 Method of preparation of NLCs 5.5.1 Hot homogenization method 5.5.2 Cold homogenization method 5.5.3 Solvent-emulsification evaporation method 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 ⇑ Corresponding author E-mail addresses: rx85priyankajain@gmail.com (P Jain), prernarahi@gmail.com (P Rahi), vikaspandeydops@gmail.com (V Pandey), saktasati@gmail.com (S Asati), drvandanasoni@gmail.com (V Soni) http://dx.doi.org/10.1016/j.ejbas.2017.02.001 2314-808X/Ó 2017 Production and hosting by Elsevier B.V on behalf of Mansoura University This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx 5.6 Characterization of NLCs 00 Patents on nanostructured lipid carriers 00 6.1 Composite sun-screening agent nano-structure, lipid carrier and its preparation method (Application Number: CN 102697663 B) 00 6.2 Formulation of anti-screening agent with nanostructured lipid carrier as its carrier system and its preparation method (Application Number: CN 102688152 A) 00 6.3 Anionic lipids and lipid nano-structures and methods of producing and using same (Application Number: US20110059157 A1) 00 6.4 Nanostructured lipid carriers containing riluzole and pharmaceutical formulations containing said particles (Application Number: US20100247619 A1, WO2008000448 A3) 00 6.5 Sunscreen formulation containing triethanolamine neutralized 2-hydroxy-4-methoxy-benzophenone-5-sulfonic acid (Application Number: US3670074 A) 00 6.6 Disappearing color sunscreen compositions (Application Number: US6007797 A) 00 6.7 Amorphous silicon film as a uv filter (Application Number: US3743847 A) 00 6.8 Use of Benzophenone Uv Filters for Preventing Tanning (Application Number: US20070219275 A1) 00 Conclusion and future perspective 00 References 00 Introduction UV rays are the component of sunlight, which exerts both positive and negative effects on living beings There are three types of UV radiations, which include UV-A (400–320 nm), UV-B (320–290 nm) and UV-C (100–290 nm) radiations (Fig A1) About 95% of UV radiations enters into the earth are about UV-A radiations and form the part of solar radiation, which penetrates deeper on skin tissues or cells as compared to UV-B radiations [1] UV-A is responsible for skin aging, wrinkles, tanning and can lead to the development of skin cancer On the other hand UV-B radiation causes sunburn, weakening of the skin inner tissues, affects human eye lens and immune system [2] It is also reported that when the human body is exposed to the UV-B rays, they are absorbed by the human cells and results DNA (deoxyribonucleic acid) impairments which will ultimately lead to death of cells An excessive exposure of UV-B radiation, leads to suppression of the immune system which in turn make the body more vulnerable to herpes simplex virus, acne, and skin lesion, etc [3] UV-C is completely absorbed by the ozone layer [4] 1.1 Skin and radiation The structure of human skin consists of three main layers (1) Epidermis (2) Dermis (3) Subcutaneous (Fig A2) Epidermis consists of five layers, namely stratum basale/germinativum, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum [5] The stratum corneum is the uppermost layer of human skin made up of flattened dead cells and hold about 25% of total epidermis In the stratum corneum due to continuous proliferation of keratinocytes, corneocytes are formed which are covered by Fig A2 Effect of UV radiation on human skin cornified protein [6] Corneocytes tightly bound together to form a barrier of the skin Proliferating keratinocytes releases lipid in this layer which make up the lipid barrier of the skin [7] In stratum granulosum layer ‘‘Cornification” takes place which is a unique process of differentiation and programmed death of the cell in keratinocytes Next layer, i.e stratum spinosum consists of immune cells (Langerhens cells) Langerhans cells are responsible for the protection against the infections These cells present about 3–6% in the epidermis excluding the stratum corneum and over expressed in stratum spinosum They play an important role in immunity in several diseases and involved in maintaining the immune homeostasis in skin by activating skin resident regulatory T Cells [8,9] The deepest layer, stratum basale/germinativum is the most germinative part of the epidermis, which shows the highest mitotic activity This layer consists of various cells, such Fig A1 Schematic representation of various layers of human skin and penetration of UV radiation to the various layers of human skin Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx as pigment producing cells known as melanocytes and merkel cells (touch receptor) [10] Next to the epidermis is the dermis layer of the skin, which provides the mechanical stability to the skin Dermis is enriched with blood vessels and lymphatic vessels along with hair follicles, sweat glands and sebaceous glands Cells such as mast cell, lymphocytes and macrophages are also observed in the dermis Beneath the dermis, subcutaneous layer is found, which is attached to the bones and muscles As similar to the dermis, this layer is also enriched with blood vessels and nerves, but as they are bigger as compared to the dermis and consists of adipose tissue, which provides mechanical protection Fibroblasts, (responsible for the production of extracellular matrix and collage) are also present in this layer and is responsible for maintaining the structural integrity within the connective tissue by secreting extracellular matrix precursors required for the formation of the connective tissue and various fibres [11] Adverse effects of UV radiations If the spectrum of radiation is observed closely in concern to the adverse effects, UV-C is completely washed out by a protective shield of the ozone layer and UV-A and UV-B creates major problems to human Some of the adverse effects of these radiations are discussed below 2.1 Sunburn (erythema) and tanning Sunburn is mostly observed in light skin individuals The increased blood flow at dermis due to UV radiations is responsible for sunburning Further exposure also leads blister and edema [12] Sunburn is usually seen after 24 h of exposure, caused predominantly by UV-B and short-wavelength UV-A Sunburn is related to molecular and cellular changes of inflammatory cells in the dermis i.e activation of mediators of inflammation such as chemokines, cytokines, prostaglandins, histamine, and nitric oxide The severity of sunburn depends on the action of the spectrum UV-B is much more energetic than UV-A; therefore very small exposure to UV-B radiation is responsible for the majority of the erythemal response Tanning is one of the common effects that are observed mainly due to the elevated response of the melanocytes, which resides in the basal cell layer [13] Melanin is a complex polymer of tyrosine derivatives, which is produced by melanocytes and packaged in melanosomes Melanosomes consist of two pigments that are responsible for skin colour, that is eumelanin (brown/black pigment) and pheomelanin (yellow/red pigment) Skin colour is decided by the amount of these two pigments within melanosomes [14] Tanning, darkening of skin occurs due to the UV rays exposure of skin for a few hours or days, involves three phases which are (a) immediate pigment darkening (b) persistent pigment darkening and (c) delayed tanning Immediate pigment darkening is observed within few minutes of UV exposure Persistent pigment darkening is observed after 1–2 h of exposure to UV rays and may last for 3–5 days and delayed tanning are seen after 2–3 days of exposure Among all the three, delayed tanning effect lasts for several weeks to months because of the synthesis of new melanin occurs during this phase Although, tanning depends on the time of UV exposure and the individual’s skin type [15] 2.2 Immune response UV radiation also affects the immune system Langerhens cells (LC) present in the skin are an element of the immune system which on interaction with UV radiation leads to specific responses i.e delayed type hypersensitivity, contact hypersensitivity etc Kripke et al, 1992 reported that DNA damage is the main cause of delayed and contact type hypersensitivity [16] 2.3 Skin photoaging Human skin consists of collagen fiber and various other proteins which contribute to the formation of extracellular matrix Complex network of collagen prevents deformation and elastic fiber provides elasticity to the skin On the other side UV radiation induces oxidation and the consequential reactive oxygen species (ROS) affect the expression of several key transcription factors especially activator protein (AP-1) and Transforming Growth Factor-b (TGF-b) AP-1 and TGF-b triggers the synthesis of matrix metalloproteases (MMP) which degrades dermal collagen and affects other skin molecules It also affects the elasticity of the skin which, leads to photoaging and it is identified by wrinkling of skin, persistent hyper pigmentation, roughness, and irregular pigmentation When radiation UV-A and UV-B are compared in case of skin photoaging, UV-A photons are more energetic and most responsible for skin photoaging, sun burning, and tanning etc [17] This whole process is summarized with the help of Fig A2 2.4 Skin cancer Skin cancer is the result of mutations induced by UV radiations Genes involved in the development of skin cancer are (1) p53, which is involved in tumor suppression, induction of DNA repair as well as apoptosis (2) patched gene, involved in regulation of cell proliferation and differentiation (3) ras (retrovirus-associated DNA sequences), involved in protooncogenes in cell membranes The number of investigations has detected p53 gene mutation in Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC) and Actinic ketososis UV exposure involved in the development of BCC is detected by patched (Ptc) mutation Ptc gene works by repressing the activity of gene which are involved in cell growth and differentiation This is also possible by the opposition of hedgehog (hh) gene activity Hedgehog gene is one which encodes for signaling protein that induces cell growth and differentiation [18,19] 2.5 Eye diseases UV rays cause deleterious effects on the eye which may include cataract, pterygium, and photokeratitis etc Cataract which is a cloudiness of the lens inside the eye is a major cause of blindness worldwide Pterygium is a development of tissue on the white of the eye that may extend onto the clear cornea so responsible for blocking vision Photokeratitis is caused by excessive UV-B exposure of the cornea results in temporary loss of vision [1] All these are the detrimental effects of UV exposure The use of protective clothing, avoiding sun exposure, and the application of sunscreen is the most common practice to protect the exposure from excessive sun rays Out of these, the application of sunscreens remains the most popular protection used by the public There are various sunscreen agents that effectively work to protect the skin from the harmful effect of UV radiation are discussed in the following section Sunscreen agents Skin which is largely affected by the solar radiations has its own mechanism to combat its harmful effect of UV by the perforation of the stratum corneum and increased melanin secretion These two mechanisms are not sufficient to prevent or subside solar radiation effects as a result the use of sunscreen is now become the most popular method which is used by a large population of the society Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx Fig A3 Diagrammatic representation of the chemical sunscreen mechanism of action Fig A4 Diagrammatic representation of the physical sunscreen mechanism of action [20,21] In the last few years sunscreen products are introduced in the cosmetic world to protect the skin from the harmful effects of UV rays Sunscreen products consist of both organic as well as inorganic UV blockers out of which organic sunscreen compounds remains on the upper epidermis and absorbs solar radiations, whereas inorganic compounds reflects and scatter the radiations Various broad spectrum sunscreen agents are incorporated in different formulations such as gels, lotions, creams, ointments and hydrogels by various scientists [22] To show its maximum efficiency an ideal sunscreen agent should have certain properties included (a) Neutral (b) Non- toxic (c) Compatible with various adjutants (d) Effective at 200–400 nm wavelength (e) Photostable (f) Non-irritant (g) No systemic effect Nowadays UV exposure and its harmful effects are inescapable Therefore, these sunscreen agents have proven excellent in preventing the damaging effects of UV radiations Sunscreen agents or UV blockers are broadly divided into two groups (1) Chemical sunscreens (2) Physical sunscreens 3.1 Chemical sunscreens (Organic) Chemical sunscreens are the agents which absorb UV radiation and convert them into a harmless energy which does not have any damaging effects on the skin as shown in (Fig A3) Their action is restricted to the superficial layer of the skin rather than the systemic action Molecules grouped in this category are always found superior to that of the physical ones as they are easily applied and effectively interact with the UV radiations But due to penetration into the superficial part of skin, may leads some of the adverse effects upon regular use Chemical (organic) sunscreens works by absorbing high-energy UV rays to protect from these harmful rays They are called as chemical sunscreen because chemical changes will be there in sunscreens molecules to prevent UV radiation reaching the skin [23] Examples include para-aminobenzoic acid (PABA) and PABA esters, salicylates, cinnamates, benzophenones etc 3.2 Physical sunscreens (Inorganic) These are the sunscreen which forms layer over the skin and reflects the incident solar radiations as shown in Fig A4 Physical (inorganic) sunscreens work by scattering the microparticles in the upper layers of skin, which may able to divert the optical pathway of photons (of UV radiation) Physical phenomena, such as scattering and reflection of radiation are involved in the protection of the skin from the UV radiation Examples include titanium dioxide, zinc oxide, iron oxide, kaolin etc., which are inert and non-irritant substances The most common inorganic UV filters include titanium dioxide (TiO2) and zinc oxide (ZnO) [23–25] Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx Table A1 FDA approved sunscreen agents U.V Blockers Range covered (nm) Description Para amino benzoic acid (PABA) 290–340 Sulisobenzone(Benzophenone-4) 290–340 3-Benzylidene camphor 290–320 Bemotrizinol(BEMT) 290–340 Butyl Methoxydibenzoylmethane (Avobenzone) 340–400 Camphor benzalkonium methosulphate 290–340 Diethylamino hydroxybenzoyl hexyl benzoate Diethylhexyl Butamido Triazone 340–400 Drometriazole trisiloxane (silatriazole; Mexoryl XL) Cinoxate 290–340 Effective UV-B filters when used in a 5% concentration in 50–60% alcohol base It penetrates deep into the dermis, acidic in nature Current use in sunscreen formulations is limited due to its in vitro carcinogenicity and allergic reactions (contact and photoallergic) [27] It is a broad spectrum sunscreen agent approved by the FDA in a concentration of 5% Highly stable and strong oxidizing agent Sulisobenzone is water insoluble in its acid form [27] 3-Benzylidene camphor is used as a sunscreen agent at levels up to 2%; highly stable The dermal absorption of the 3-Benzylidene camphor is very low It is a potential endocrine disruptor and also shows multiple hormonal activities Soluble in absolute alcohol and isopropanol Insoluble in water [27] Bemotrizinol absorbs ultraviolet radiations in both UV-A and UV-B range It is oil soluble chemical Highly photostable Its presence in formulation also protects less photostable UV blockers, such as avobenzone [27] Highly effective for UV-A radiations It is used in combination with other sunscreen agents to cover a broad spectrum of UV radiation Concentrations up to 3% is used as an effective sunscreen agent Insoluble in water, soluble in ethanol [27] Camphor benzalkonium methosulphate is used as UV-filter at a maximum concentration of 6.0% Mild irritating potential to the eye when used undiluted or as a 20% aqueous solution It has a borderline margin of safety [27] An effective UV-A filter; oil-soluble yellow liquid Widely used as sun protective agent at concentrations up to 10% It has good compatibility with other UV filters and other ingredients High Photostability [27] In European country, it is used as a UV filter in cosmetics and personal care products at a maximum concentration of 10% Although FDA approved up to percent only At 3% concentration, it is efficient and is not irritant as well as non sensitizer, photosensitizer or photoirritant [27] Photostable broad spectrum UV filter An allergic reaction is rarely seen [27] Dioxybenzone 290–340 Ecamsule (Mexoryl SX) 340–400 Homomenthyl salicylate (Homosalate) 290–320 Meradimate (Menthyl Anthranilate) Octocrylene 340–400 290–320 Ethylhexyl methoxycinnamate and octinoxate IMC (Amiloxate) 4–4-Methylbenzylidene camphor (enzacamene) Methylene-bis-benzotriazolyl tetramethylbutylphenol (Tinasorb M) 290–320 340–400 290–320 290–320 290–320 290–340 Ethylhexyl Triazone 290–320 Ethylhexyl salicylate(octylsaliclate; octisalate) Oxybenzone 290–320 Padimate O 290–320 Titanium Dioxide 290–340 Zinc oxide 290–340 290–340 A light yellowish liquid, insoluble in water, but soluble in glycerol and various vegetable oil Covers the spectrum of UV-B [23] Broad spectrum UV Blocker from the family of benzophenone used in various other cosmetic formulations, but it is reported as sensitizing agent [23] Photostable Has a good safety profile as compared to other UV-A blockers It is not absorbed by the skin and effectively covers the entire spectrum of UV-A [23] Salycilate derivative, oil soluble Has a good safety profile, but used in combination with other UV blocker for effective sun blocking activity Covers, UV-B spectrum Up to 10% w/w used as a sun screen agent [23] Rarely used anthranilates and it covers only a specific spectrum of UV-A [23] Effective for UV-B range Photostable, moisturizing effect is observed due to its ethyhexol portion of the molecule Used in combination with other UV blockers [23] Used for the protection against UV-B radiation Water insoluble cinnamate Used in combination due to its instability [23] Insoluble in water, soluble in ethanol and other organic solvents, effective UV-B sunscreen agent, safe [23] Ability to protect the skin against UV-B radiation It also showed estrogenic effect [23] Absorb both UV-A and UB-A radiation It is a new class of UV filters that combine the properties of both UV conventional filters (organic and inorganic) – it scatters, reflects and absorbs UV light It is colorless organic microfine particles and photostable Very less systemic absorption [23] Absorb UV light at maximum 5% concentration Oil-soluble UV-B filter Insoluble in water, which makes it suitable for water-resistant products It has excellent photostability[23] Octyl salicylate is an oil soluble sunscreen agent, efficient for UV-B radiation Salicylates are weak UV-B absorbers Used in combination with other UV filters Has a good safety profile [23] Broad spectrum UV filters from the family of benzophenone Most popular UV blocker Photostable Carcinogenic activity is also observed hence its regular use is still argued [28] PABA derivative, compatible with various cosmetic ingredients Used in combination with other UV blocker to attain greater and effective sun blocking agent [28] A physical sunscreen agent Photostable Less reactive in nature Used in micronized and nanosized for their maximum efficacy [28] Used with titanium dioxide in majority of marketed formulation zinc oxide is the only sunscreen ingredient that appears on more than one FDA monograph Microfine zinc oxide effective in the UV-A protection [28] The molecules of these physical sunscreens are smaller in size, which helps in the reflection and scattering of the radiation [26] Skin can be protected from UV-A and UV-B by both inorganic and organic UV filters Some of the sunscreen agents which are approved by Food and Drug Administration (FDA) are enlisted in Table Novel drug delivery systems and formulations Nanotechnology is one of the flourishing technologies in the pharmaceutical industries in which drug and their delivery systems are designed and structured by controlling their size in nano range The delivery system bearing sunscreen/UV filters must be suitable enough to deliver sun protectants to the predetermined site in the sufficient amount [29] An ideal drug delivery system must have following qualities[30] a) Maximum drug loading capacity b) Enhance drug stability c) Provide targeted and sustained action The nano ranged UV filters provide better action with long lasting effects The utilization of the nano sized material was increased due to the fact that nano ranged substance have different properties than larger sized particle, and have altered physiochemical Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx properties The carrier systems may be modified according to the use and the cosmetic drugs/agents to be delivered [31] Various drug carrier systems used for sunscreen agents and basically for topical drug delivery systems includes (1) Liposomes (2) Transferosomes (3) Niosomes (4) Ethosomes (5)Solid Lipid Nanoparticles, NLCs etc [32–33] 4.1 Liposomes Liposomes are the spherical vesicles with an aqueous core in the center, surrounded by lipid layer Lipid layer is formed by phospholipids and cholesterol [34] Structurally liposomes are equipped with both lipid and aqueous phases which make them to carry both lipophilic and hydrophilic drugs Liposomes can be classified on the basis of their size which includes (a) Small unilamellar vesicles (SUVs) (b) Large unilamellar vesicles (LUVs) (c) Multilamellar vesicles (MLVs) (d) Oligolamellar (OLVs) [35] The role of phospholipids is to produce bilayer whereas, cholesterol is used to provide stability to the bilayer There are various methods adopted to prepare liposomes are lipid film hydration, solvent injection, emulsification and reverse phase evaporation method When the size of the liposomes are required to optimized then some other techniques such as sonication, extrusion and high pressure homogenization are commonly used The structural benefits of liposomes are their similarity to biological membranes of the body which helps them to easily penetrate and deliver the content The drugs, depending upon their characteristic and affinity either get into the aqueous phase or bilipid layer But the disadvantage which associated with liposomes is the low entrapment efficiency of hydrophilic cosmetic agents and unstability due to phospholipids [36] Liposomes are effective drug delivery systems for antibiotics, proteins as well as for sunscreen agents and other cosmetic agents More than 10% of the cosmetic market consists of liposomes as a drug delivery system Lipid used for the liposomes are specifically stratum corneum compatible, which helps in effectively depositing the drug topically Liposomes also provide a moisturizing effect due to the presence of skin friendly phospholipids Formulations with liposomes has good adherence to the skin surface and therefore they are not easily washed away In one study the liposome bearing Sodium ascorbyl phosphate was prepared which showed enhanced sodium ascorbyl phosphate penetration through the epidermal membrane as compared to sodium ascorbyl phosphate as in simple water solution [37] Liposomes are biodegradable and provide sustained delivery of UV blockers Toxicity effects of encapsulated agents are also minimized to a greater extent [38] Kitagawa et al prepared the cationic liposomes bearing retinoic acid by using double-chained cationic surfactant(dimethyldipalmi tylammonium) and phosphatidylcholine These cationic liposomes enhance the delivery of retinoic acid about two-fold, which indicates the potential use of the cationic liposomes for the intradermal delivery of lipophilic drugs like retinoic acid [39] 4.2 Transfersomes Various vesicular systems have already developed as an effective drug delivery system in the cosmetic industry and transferosomes is one of the such vesicular system and also known as ‘‘elastic vesicular” system The difference between liposome and transfersomes is the use of edge activator which is basically the surfactant Surfactants are used in the preparation to deform the lipid layer of vesicles This deformation induced by the added surfactant helps in the better penetration into the skin [40] Non occlusive nature enhances the effective function of transfersomes and perfect deposition of the drug [41] Due to the deformation observed in the lipid layer provide transfersomes a structural benefit to form a depot, which help in slow release of drug as well as extrude themselves from the pores of intracellular lipid of stratum corneum Transfersomes are the best vesicular systems for topical administration of various drugs which are needed to be localized An improved skin deposition and photostability was observed when a–tocopherol was administered topically in the form of transferosome [42] Another reported drugs like triamicinolone acetonide [43], oestradiol [44] and cyclosporin A [45] which are successfully encapsulated in transfersomes for topical delivery 4.3 Niosomes Niosomes are those vesicular systems which are similar to liposome, but made from nonionic surfactant and cholesterol for the formation of bilayer They are superior to other vesicular system in terms of stability and ultimately its shelf life [46] The advantage of using a nonionic surfactant in the formation of bilayer is to increase permeability and bioavailability of the drug entrapment [47] Method of preparation are same as that of liposomes, which includes sonication, extrusion etc Vesicular formulation are advantageous in cosmetic application as various ingredients such as antioxidant, fatty acids, vitamins and UV blockers are successfully encapsulated either in the bilayer or aqueous core The content of the carrier resides on the skin surface, i.e the upper layer of the stratum corneum and provide effective localized action Drugs such as enoxacin [48], b-galactosidase [49], interferon a, cyclosporine [50], estradiol [51], have also been delivered transdermally through niosomes 4.4 Ethosomes As similar to liposomes and niosomes, ethosomes are also composed of phospholipids, but vesicles are prepared with the help of ethanol and water The size of vesicular systems depends on the concentration of phospholipids and ethanol [52] The striking feature of these carrier systems is the use of ethanol, which allows the entrapment of the different nature of drugs such as hydrophilic, lipophilic and amphiphilic molecule [53] The cholesterol is the fluidity buffer used in liposomes as well as in ethosomes Ethanol helps in deformation or disruption of the upper layer of skin and provides the entry of ethosomes to enhance drug delivery of trihexylphenidyl hydrochloride [54] testosterone [55], acyclovir [56] ammonium glycyrhizinate [57] and bacitracin [58] The release of drug in the deep layers of the skin and transdermal absorption is the result of fusion of ethosomes with skin lipids and drug release is observed at various points along the penetration pathway [59] Improved therapeutic effectiveness and permeation of antibiotics and antibacterial from these vesicular systems are also reported [60,61] 4.5 Solid lipid nanoparticles (SLNs) SLNs are the nano sized lipophilic matrix in which drug is effectively encapsulated Lipids utilized in the preparation of SLNs Fig A5(a) Imperfect NLCs Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx Fig A5(b) Amorphous NLCs (c) Multiple NLCs NLCs are one such kind of nano-carriers that has conquered a better place than other carrier systems mainly in topical preparations The structural aspect of NLCs due to which higher loading capacity is observed can be justified by the fact that a larger fraction of drugs are soluble in liquid lipids and when solid and liquid lipids are blended together the liquid lipids accommodated in the core space surrounded by solid lipids, in this way drugs are accurately encapsulated [71] Identified structure of NLCs obtained by matching various compositions as well as parameters are: (1) Imperfect NLCs (2) Amorphous NLCs (3) Multiple NLCs 5.1 Imperfect NLCs These NLCs are produced by the mixing of solid lipids and chemically vary different liquid lipids To increase the drug loading capacity, glycerides composed of different fatty acids are used Because of the distance in the fatty acid chain leads to the formation of imperfections in the crystal (Fig A5(a)) The imperfections are the result of the incompatibility between lipids and intentionally utilized for the achievement of higher loading capacity, hence thus makes important to choose incompatible lipids [72] Fig A5(c) Multiple NLCs 5.2 Amorphous NLCs include fatty acids, waxes, glycerides, triglycerides etc Method of preparation of SLNs includes hot homogenization, high pressure homogenization, high shear homogenization, ultra sonication, melt dispersion, microemulsion dilution, microemulsion cooling, coacervation, solvent injection, solvent evaporation, supercritical fluid extraction of emulsion and spray drying etc SLNs are termed as the first generation, lipid based nanoparticles and have wide applicability in pharmaceutical medicine due to chemical stability, physical stability and biocompatibility with large number of drugs For providing stability to the system, emulsifiers such as poloxamer 188, polysorbate 80, fatty acid ester etc are used [62] Cold homogenization is better suited for heat sensitive compounds or substances which can be easily partitioned from the melted lipid [63] It is well reported that the therapeutic active substance such as clobetasol propionate [64], antiandrogen etc [65] was delivered successfully with SLNs The formulation of SLNs was found to be localized in the outer layer skin with minimum systemic circulation Retinol, tocopherol and coenzyme Q10 compounds are protected from degradation when successfully incorporated into SLNs [66] SLNs have several other advantages such as modified release of the active compound, lipophilic and hydrophilic drugs incorporated easily and increased in skin hydration However, drawbacks associated with SLNs are uncontrolled drug expulsion from the carrier and limited drug loading capacity To overcome these limitations, a second generation of lipid nanoparticles, NLCs, has been developed [67,68] The crystallization process leads to the expulsion of drugs and therefore NLCs which are solid are preferred over crystalline one with the use of special lipids (hydroxyoctacosanylhydroxy-stea rate, isopropylmyristate) by which particle acquires solid state rather than crystalline (Fig A5(b)) [73] 5.3 Multiple NLCs Multiple NLCs are prepared by mixing solid lipids with large amount of oil (liquid lipids), small nanocompartments within nanoparticles are created by a phase separation process during particles production The solid matrix of the lipid nanoparticles contains tiny liquid nanocompartments of oil In these oil compartments the drug has high solubility (Fig A5(c)) The oil compartments formed are surrounded by solid lipids and hence controlled drug release was observed [74] 5.4 Advantages over other lipid carriers Comparison between NLCs and SLNs reflects that SLNs require pure solid lipids, which leads to the formation of the perfect carrier structure, whereas in the case of NLCs imperfect/distorted structure was observed, which allows more of the drugs to be fitted in Nanostructured lipid carriers (NLCs) For the delivery of drug and cosmetics, further improvement in lipid based carrier systems, paved way to a new generation of SLNs, which was termed as nanostructured lipid carriers (NLCs) [69] NLCs composed of both solid and liquid lipids Liquid Lipids (oil) incorporation causes structural imperfections of solid lipids due to which a perfect crystalline structure is deviated to form a crystal lattice with many spaces The spaces are assumed to be imperfection, but these are the actual spaces where drug homes itself Hence the liquid lipid being used, determines the state of nanocarriers as well as its loading capacity [70] Release pattern of the active constituents is also based on the blend of solid and liquid lipids Fig A6(a) Flow chart of the hot homogenization method Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx 5.5.1 Hot homogenization method High pressure homogenization is the conventional method for the fabrication of NLCs The advantages associated with this method includes, short production time, limited use of various other chemicals and easy scale up In this method active pharmaceutical ingredient is dissolved in a mixture of melted lipids, the resulted mixture is quickly dispersed in aqueous emulsifier with high speed stirring Temperature is maintained constant during the whole process The prepared emulsion is subjected to high pressure homogenization with high ultrasonic intensity which converts the emulsion to nano range emulsion Cooling is done either in cold water or by a heat exchanger and precipitate of nanoparticles is collected (Fig A6(a)) Disadvantage associated with this method is the degradation of heat sensitive ingredients due to the temperature [81] Fig A6(b) Flow chart of cold homogenization method the imperfect site and an overall increase in the drug loading capacity was seen Liposomes and various emulsions are also studied in terms of stability of the active constituents in comparison to NLCs and it was observed that liposomes have limited protection against the chemical degradation Active drugs in case of liposomal formulations can be placed either in the aqueous core or phospholipids bilayer and if the drug partitions in the phase which is incompatible for drug, degradation may occur Some experiments were performed to demonstrate stability of lipid nanoparticles [75] Presently, NLCs are used as novel drug delivery system owing to its several advantages which includes solubility enhancement of poorly soluble drugs, reduces skin irritation, better physical stability, ease of manufacturing and scale-up, high entrapment efficiency of both the lipophilic s and hydrophilic drugs, controlled particle size, occlusive in nature and provide extended release of the drug [76,77,26] When topical formulations are concerned, adhesiveness is required for film formation Adhesiveness is the property of fine material which is directly related to occlusion Adhesiveness increases with decreasing particle size NLCs have enhanced adhesive property; they adhere to the skin surface which ultimately leads to the formation of a film over the skin and provide occlusion effect The occlusion can be increased by reducing the particle size or at a given particle size by increasing the number of particles i.e increasing lipid concentration Therefore, nanoparticles provide ‘‘controlled occlusion effect” Skin hydration is another important factor because it promotes penetration of the drug in the skin NLCs also maintain sufficient skin hydration by the formation of occlusive layer over the skin Other important parameters such as the size of the carriers as well as drugs which are an important tool to avoid systemic effects If the physical stability of the system is concerned, SLNs and NLCs have proven themselves far better than any other system due to the presence of solid matrix [78] NLCs are suitable carriers for the sunscreen agents because these agents are the active material place itself in the solid matrix causes delayed and prolonged drug release [79] Also the lipids utilized for NLCs act as UV filters which provides synergistic effect and because of this synergistic effect, the required quantity of sunscreen agent will decrease for sunscreen action 5.5 Method of preparation of NLCs Production of NLCs are closely related to SLNs The most common methods used for their preparation are hot homogenization method, cold homogenization method and solvent emulsification evaporation method [80] 5.5.2 Cold homogenization method As the name suggests that the temperature used in the whole process is lower than that used in a hot homogenization process which ultimately rule out disadvantage that may be produced due to heat The mixture of the lipids with the drug is rapidly cooled by the utilization of liquid nitrogen The lipid matrixes obtained are milled and then the particles are dispersed in the emulsifier solution and subsequently homogenized to produce fine particle (Fig A6(b)) Various advantages of this process over the hot homogenization process are: Thermal degradation is minimized Improved drug entrapment efficiency Uniform distribution of drug within the lipid [82] In comparison to the hot homogenization method, larger particle sizes and a broader size distribution are observed in cold homogenized method Although cold homogenization minimizes the thermal exposure of the sample, but it cannot be completely avoidable as melting of the lipid/ drug mixture is required in the initial step 5.5.3 Solvent-emulsification evaporation method In this method, lipids and drugs are mixed with certain solvent and resulted mixture is quickly dispersed in the emulsifier solution and the solvent is evaporated by the reduction in pressure which leaves behind required nanoparticles[83] Some of common lipids used for the preparation of NLC’s are discussed with their structure and properties in Table 5.6 Characterization of NLCs Characterization is an important aspect to understand nanomaterials and their possible applications Nanostructures have a physical size, which is the important characteristic for their applications Structure and properties of any nanoparticles formulations depend on the environment exposed, which leads to structural transformation, agglomeration, etc These changes in the nanostructure have to be identified and studied for their better implications Table describes the characterization parameters required for NLCs Patents on nanostructured lipid carriers 6.1 Composite sun-screening agent nano-structure, lipid carrier and its preparation method (Application Number: CN 102697663 B) The invention discloses a novel sunscreen composite nanostructured lipid carriers, the carrier loaded with ethylhexyl triazone and diethylamino hydroxylbenzoyl hexyl benzoate Nanostructured lipid carrier system was prepared according to weight percentage of ethylhexyl triazone 1–10% and diethylamino hydroxyl benzoyl hexyl benzoate 2–20% and 3–15% of emulsifier The rest is deionized water; the composition material is a mixture of solid lipid Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx Table A2 Lipids Used in the NLCs preparation Structure A Liquid lipid Medium Chain Triglyceride/Caprylic Triglyceride Corn Oil Description Fatty acid with 6–12 carbon atom and glycerol as backbone Stable against oxidation, used as solvent, emulsifier and vehicle These are the lipids with different molecular weight and are easily digestible [84] Natural oil and an antioxidant, protects the drug from oxidation due to high unsaturation Highly viscous [85] a-Tocopherol Yellowish viscous liquid, soluble in acetone, ethanol and chloroform They are unstable in UV light and used as antioxidant and vitamin E supplement [86] Squalene‘ Translucent liquid Not used in high concentration It is a good moisturizer and less susceptible to oxidation It is an important part of steroid synthesis [87] Oleic Acid Yellowish oil, water insoluble It has low viscosity On exposure to air it oxidizes It has been reported to effectively penetrate into the skin and also through hair follicle [88] B Solid lipid Cetyl Palmitate Stearic Acid Tristearin Ester of palmitic acid Naturally occurs in the wax found in the skull of sperm whale Water insoluble, pharmaceutically used for skin conditioning and emollient action Also used due to its property of excellent film former [89] Saturated fatty acid with 18 carbon backbone Soluble in acetone and slightly soluble in ethanol Ability to penetrate skin and even mucous membrane make good candidate for NLC preparations [90] White, odorless powder, insoluble, emollient in nature, solvent and skin conditioning agent Controls viscosity of the formulation [91] Propylene Glycol Monostearate Soluble in water, colorless liquid Used as humectants and solvent in various formulations It is a common ingredient in personal care product [92] Glyceryl Monostearate It is glycerol ester of stearic acid Used as emulsifier as well as thickening agent It is nontoxic and non-irritant [93] and liquid lipid material Lipid material is selected from at least one of the following compounds: acetylation monoglycerides, glyceryl stearate, grape seed oil, glycerol L The prepared ethylhexyl triazone and diethylamino hydroxyl benzoyl hexyl benzoate loaded NLC can be effectively used in cosmetics with excellent properties such as stability, simple method of preparation and reproducible results 6.2 Formulation of anti-screening agent with nanostructured lipid carrier as its carrier system and its preparation method (Application Number: CN 102688152 A) The invention discloses about the composition of anti-screening agent bearing nanostructured lipid carrier The formulation of nanostructured lipid carrier comprises the following components in percentage by weight: 3–40% of anti-screening agent, 2–15% of emulsifier, 2–20% of lipid material and the water UV-A anti-screening agent is avobenzone and consists of at least one of the following compounds: octocrilene and iso-octyl p-methoxycinnamate The composition of lipid material is the mixture of solid lipid material and liquid lipid material The lipid material consists of at least one of the following compounds: glyceryl triacetate, diethyl sebacate, caprylic/capric triglyceride, acetylate monoglyceride, diisopropyl sebacate, glyceryl monostearate, and carnauba wax The preparation method is simple and good repeatability The nanostructured lipid carrier is used for preparing antiscreening cosmetics 6.3 Anionic lipids and lipid nano-structures and methods of producing and using same (Application Number: US20110059157 A1) This invention explained the development of anionic lipid and liposome/lipid nanostructures as well as study the effect of various anionic lipids on hemoglobin encapsulation Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 10 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx Table A3 Characterization parameters for NLCs S NO Parameter Instrument Importance Particle size and charges Particle size analysis is important for quality assurance and in consideration of stability aspect [94] Particle Morphology Encapsulation efficiency Thermal Analysis Interaction between drug and exipient Drug release pattern Laser Diffractometry Photo Correlation spectroscopy (PCS) Zetasizer Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) Atomic Force Microscopy (AFM) Centrifuge Ultra centrifuge HPLC(High Performance Liquid Chromatography) Differential Scanning Calorimetry X-ray Diffraction Fourier transform infrared (FTIR) spectroscopy In-vitro drug release study Drug availability in body In vivo study These high magnification microscopy provides information about surface as well as a three dimensional structure of the nanoparticle Controlling the morphology of the nanostructure directly affects the properties of the material such as drug loading efficiency, drug release potential etc [95] Measurement of the active ingredient encapsulated is necessary to validate the delivery system for being appropriate in carrying the drug to the target site that too in sufficient quantity [96] Thermal stress leads crystal changes which indirectly affect the particle size and drug loading efficiency, this method also provides information regarding the maximum temperature in which the delivery system is stable and retain to be solid in nature [97] Characteristic peaks of drug give the information of any possible interaction between the drug and excipients in NLCs formulation [98] Provide the drug release profile from different formulations and help in determining the release of drug from system and its availability [99] Gives the information about the better bioavailibilty of poorly water soluble drugs and proper availability of drugs in different tissues [100] 6.4 Nanostructured lipid carriers containing riluzole and pharmaceutical formulations containing said particles (Application Number: US20100247619 A1, WO2008000448 A3) This invention relates to nanoparticles consisting of riluzole trapped in lipids, and their use to prepare medicinal products for the treatment of Amyotrophic Lateral Sclerosis and Multiple Sclerosis 6.5 Sunscreen formulation containing triethanolamine neutralized 2-hydroxy-4-methoxy-benzophenone-5-sulfonic acid (Application Number: US3670074 A) This invention describes an active sunscreen ingredient which is having the composition of 2-hydroxy-4-methoxy-benzophe none-5-sulfonic acid, neutralized with triethanolamine, and formulated with various compatible vehicles They describe the production of effective sunscreens for human use 6.6 Disappearing color sunscreen compositions (Application Number: US6007797 A) This invention describes the colored sunscreen emulsion which includes an oil-soluble phase, at least one sunscreen active agent, water, and an emulsifier The oil-soluble phase comprises about 0.0005–0.5% by weight of the complete emulsion of at least one oil-soluble dye The dye imparts a color other than white to the sunscreen emulsion 6.7 Amorphous silicon film as a uv filter (Application Number: US3743847 A) This invention describe the morphous silicon film as a uv filter and use of a thin amorphous silicon film as a narrow-band rejection filter protect from to UV light 6.8 Use of Benzophenone Uv Filters for Preventing Tanning (Application Number: US20070219275 A1) The invention describes the use of Benzophenone as a UV filters Conclusion and future perspective NLCs seem to be suitable delivery systems intended for topical administration of drugs and cosmetic agents NLCs are considered as a second and smarter generation of nanoparticles, which has enhanced and improved properties for drug loading and stability of drug incorporation throughout the storage period NLCs are considered useful for the administration of lipophilic agents Thus the NLCs have very promising future for the delivery of drugs and cosmetic agents In future, the pharmaceutical and cosmetic companies will prefer to formulate NLCs because of their various advantages but pre-clinical and clinical studies are needed to be performed to establish formulations in the market on the basis of low risk/high benefit ratio as compared to high risk/low benefit ratio References [1] Gallagher RP, Lee TK Adverse effect of ultraviolet radiation: a brief review Prog Biophys Mol Biol 2006;92:199 [2] Matsumura Y, Ananthaswamy HN Toxic effect of ultraviolet radiation on the skin Toxicol Appl Pharmacol 2001;195:298–308 [3] Hönigsmann H, Szeimies RM, Knobler R, Fitzpatrick TB, Pathak MA, Wolff K Photochemotherapy and photodynamic therapy Fitzpatrick’s dermatology in general medicine fifth ed New York: McGraw-Hill; 1999 p 2880–900 [4] Pathak SK, Mason NJ Our shrinking ozone layer Resonance 2002;7 (12):71–80 [5] Gauglitz GC, Schauber J Skin architecture and function In: Dermal replacement in general, burn, and plastic surgery Springer-Verlag; 2013 p 1–11 [6] Radner FP, Fischer J The important role of epidermal triacylglycerol metabolism for maintenance of the skin permeability barrier function Biochim Biophys Acta 2014;1841(3):409–15 [7] Meckfessel MH, Brandt S The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products J Am Acad Dermatol 2014;71(1):177–84 [8] Stoitzner P The Langerhans cell controversy: are they immunostimulatory or immunoregulatory cells of the skin immune system? Immunol Cell Biol 2010;88(4):348 [9] Seneschal J, Clark RA, Gehad A, Baecher-Allan CM, Kupper TS Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells Immunity 2012;36(5):873–84 [10] Lavker RM, Sun TT Epidermal stem cells J Invest Dermatol 1983;81(s 1):121–7 [11] McGrath JA, Eady RA, Pope FM Anatomy and organization of human skin In: Burns T, Breathnach S, Cox N, Griffiths C, editors Rook’s textbook of dermatology p 25–8 [12] Parrish JA, Jaenicke KF, Anderson R Erythema and melanogenesis action spectra of normal human skin Photochem Photobiol 1982;36(2):187–91 [13] Pathak MA, Jimbow K, Parrish JA, Kaidbey KH, Kligman AL, Fitzpatrick TB Effect of UV-A, UV-B and psoralen on in vivo human melanin pigmentation Pigment cell 1976;3:291–8 Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx [14] Cichorek M, Wachulska M, Stasiewicz A, Tyminska A Skin melanocytes: biology and development Postepy Dermatol Alergol 2013;30(1):30–41 [15] Brenner M, Hearing VJ The protective role of melanin against UV damage in human skin Photochem Photobiol 2008;84(3):539–49 [16] Kripke ML Immunological unresponsiveness induced by ultraviolet radiation Immunol Rev 1984:87–102 [17] Kochevar JE Molecular and cellular effect of UV radiation relevant to chronic photodamage In: Bilchrest BA, editor Photodamage M.A.: Blackwell; 1995 p 51–8 [18] Ziegler A, Jonason AS, Leffellt DJ, Simon JA, Sharma HW, Kimmelman J, et al Sunburn and p53 in the onset of skin cancer Nature 1994;372(6508): 773–6 [19] Narayanan DL, Saladi RN, Fox JL Ultraviolet radiation and skin cancer Int J Dermatol 2010;49:978–86 [20] Pathak MA Sunscreens: topical and systemic approaches for protection of human skin against harmful effects of solar radiation J Am Acad Dermatol 1982;7(3):285 [21] Jablonski NG, Chaplin G The evolution of human skin coloration J Hum Evol 2000;39(1):57–106 [22] Morabito K, Shapley NC, Steeley KG, Tripathi A Review of sunscreen and the emergence of non-conventional absorbers and their applications in ultraviolet protection Int J Cosmet Sci 2011;33(5):385–90 [23] Latha MS, Martis J, Shobha V, Shinde RS, Bangera S, Krishnankutty B, et al Sunscreening agents: a review J Clin Aesthet Dermatol 2013;6(1):16 [24] Lademann J, Schanzer S, Jacobi U, Schaefer H, Pflu F, Driller H, et al Synergy effects between organic and inorganic UV filters in sunscreens J Biomed Opt 2005;10(1):014008 [25] Saewan N, Jimtaisong A Natural products as photoprotection J Cosmet Dermatol 2015;14(1):47–63 [26] Jain SK, Jain NK Multiparticulate carriers for sun-screening agents Int J Cosmet Sci 2010;32(2):89–98 [27] Barel AO, Paye M, Maibach HI, editors Handbook of cosmetic science and technology CRC Press; 2014 [28] Tuchinda C, Lim HW, Osterwalder U, Rougier A Novel emerging sunscreen technologies Dermatol Clin 2006;24(1):105–17 [29] Nash JF, Tanner PR, Matts PJ Ultraviolet A radiation: testing and labeling for sunscreen products Dermatol Clin 2006;24(1):63–74 [30] Gabard B, Elsner P, Surber C, Treffel P, editors Dermatopharmacology of topical preparations: a product development-oriented approach Springer Science & Business Media; 2011 [31] Raj S, Jose S, Sumod US, Sabitha M Nanotechnology in cosmetics: opportunities and challenges J Pharm Bioall Sci 2012;4(3):186 [32] Wu X, Guy RH Applications of nanoparticles in topical drug delivery and in cosmetics J Drug Deliv Sci Technol 2009;19(6):371–84 [33] Kaur IP, Kapila M, Agrawal R Role of novel delivery systems in developing topical antioxidants as therapeutics to combat photoageing Ageing Res Rev 2007;6(4):271–88 [34] Touitou E, Junginger HE, Weiner ND, Nagai T, Mezei M Liposomes as carriers for topical and transdermal delivery J Pharm Sci 1994;83 (9):1189–203 [35] Fang J Nano-or submicron-sized liposomes as carriers for drug delivery Chang Gung Med J 2006;29(4):358 [36] Brandl M Liposomes as drug carriers: a technological approach Biotechnol Annu Rev 2001;7:59–85 [37] Focˇo A, Gašperlin M, Kristl J Investigation of liposomes as carriers of sodium ascorbyl phosphate for cutaneous photoprotection Int J Pharm 2005;291 (1):21–9 [38] Lasic DD Application of liposome In: Lipowsky R, Sackmann E, editors Handbook of Biological Physics: Structure and Dynamics of Membrane Amsterdam: Elsevier Science BV; 1995 p 491–591 [39] Kitagawa S, Kasamaki M Enhanced delivery of retinoic acid to skin by cationic liposomes Chem Pharm Bull 2006;54(2):242–4 [40] Van den Bergh BA, Vroom J, Gerritsen H, Junginger HE, Bouwstra JA Interactions of elastic and rigid vesicles with human skin in vitro: electron microscopy and two-photon excitation microscopy BBA Biomembr 1999;1461(1):155–73 [41] Cevc G Material transport across permeability barriers by means of lipid vesicles Handbook of biological physics 1995;1:465–90 [42] Chapman SJ, Walsh A Desmosomes, corneosomes and desquamation An ultrastructural study of adult pig epidermis Arch Dermatol Res 1990;282 (5):304–10 [43] Cevc G, Blume G Biological activity and characteristics of triamcinoloneacetonide formulated with the self-regulating drug carriers, TransfersomesÒ BBA Biomembr 2003;1614(2):156–64 [44] El Maghraby GM, Williams AC, Barry BW Oestradiol skin delivery from ultradeformable liposomes: refinement of surfactant concentration Int J Pharm 2000;196(1):63–74 [45] Guo J, Ping Q, Sun G, Jiao C Lecithin vesicular carriers for transdermal delivery of cyclosporin A Int J Pharm 2000;194(2):201–7 [46] Uchegbu IF, Vyas SP Non-ionic surfactant based vesicles (niosomes) in drug delivery Int J Pharm 1998;172(1):33–70 [47] Jayaraman SC, Ramachandran C, Weiner N Topical delivery of erythromycin from various formulations: an in vivo hairless mouse study J Pharm Sci 1996;85(10):1082–4 [48] Fang JY, Hong CT, Chiu WT, Wang YY Effect of liposomes and niosomes on skin permeation of enoxacin Int J Pharm 2001;219(1):61–72 11 [49] Raghavachari N, Fahl WE Targeted gene delivery to skin cells in vivo: a comparative study of liposomes and polymers as delivery vehicles J Pharm Sci 2002;91(3):615–22 [50] Niemiec SM, Ramachandran C, Weiner N Influence of nonionic liposomal composition on topical delivery of peptide drugs into pilosebaceous units: an in vivo study using the hamster ear model Pharm Res 1995;12(8):1184–8 [51] Fang JY, Yu SY, Wu PC, Huang YB, Tsai YH In vitro skin permeation of estradiol from various proniosome formulations Int J Pharm 2001;215 (1):91–9 [52] Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties J Control Release 2000;65(3):403–18 [53] Touitou E, inventor; Yissum Research Development Company of the Hebrew University of Jerusalem, assignee Composition for applying active substances to or through the skin United States patent US 5,716,638 1998 [54] Dayan N, Touitou E Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs liposomes Biomaterials 2000;21(18):1879–85 [55] Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties J Control Release 2000;65(3):403–18 [56] Ainbinder D, Touitou E Testosterone ethosomes for enhanced transdermal delivery Drug delivery 2005;12(5):297–303 [57] Horwitz E, Pisanty S, Czerninski R, Helser M, Eliav E, Touitou E A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87(6):700–5 [58] Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers J Control Release 2005;106(1):99–110 [59] Godin B, Touitou E Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier J Control Release 2004;94(2):365–79 [60] Godin B, Touitou E, Rubinstein E, Athamna A, Athamna M A new approach for treatment of deep skin infections by an ethosomal antibiotic preparation: an in vivo study J Antimicrob Chemother 2005;55(6):989–94 [61] Godin B, Touitou E Erythromycin ethosomal systems: physicochemical characterization and enhanced antibacterial activity Curr Drug Deliv 2005;2(3):269–75 [62] Schäfer-Korting M, Mehnert W, Korting HC Lipid nanoparticles for improved topical application of drugs for skin diseases Adv Drug Deliv Rev 2007;59 (6):427–43 [63] Dingler A, Blum RP, Niehus H, Muller RH, Gohla S Solid lipid nanoparticles (SLNTM/LipopearlsTM) a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products J Microencapsul 1999;16 (6):751–67 [64] Müller RH, Radtke M, Wissing SA Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations Adv Drug Deliv Rev 2002;54 S131-55 [65] Santos Maia C, Mehnert W, Schaller M, Korting HC, Gysler A, Haberland A, Schäfer-Korting M Drug targeting by solid lipid nanoparticles for dermal use J Drug Target 2002;10(6):489–95 [66] Kalariya M, Padhi BK, Chougule M, Misra A Clobetasol propionate solid lipid nanoparticles cream for effective treatment of eczema: formulation and clinical implications Indian J Exp Biol 2005;43(3):233–40 [67] Wissing SA, Müller RH Cosmetic applications for solid lipid nanoparticles (SLN) Int J Pharm 2003;254(1):65–8 [68] Wissing SA, Müller RH Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration J Control Release 2002;81 (3):225–33 [69] Tamjidi F, Shahedi M, Varshosaz J, Nasirpour A Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules Innov Food Sci Emerg Technol 2013;19:29–43 [70] Müller RH, Petersen RD, Hommoss A, Pardeike J Nanostructured lipid carriers (NLC) in cosmetic dermal products Adv Drug Deliv Rev 2007;59(6):522–30 [71] Müller RH, Radtke M, Wissing SA Nanostructured lipid matrices for improved microencapsulation of drugs Int J Pharm 2002;242(1):121–8 [72] Das S, Chaudhury A Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery Aaps Pharmscitech 2011;12(1):62–76 [73] Muller RH, Jenning V Zusammensetzung, Herstellung and Verwendungeiner Suspension verfestigter, amorpher Oltropfchen Deutsche Patentanmeldung 1999;12:199–383 [74] Jenning V, Gohla SH Encapsulation of retinoids in solid lipid nanoparticles (SLN) J Microencapsul 2001;18(2):149–58 [75] Jenning, Feste V Lipid-Nanopartikel (SLN) als Trägersystem für die dermale applilkation von Retinol [Ph.D thesis] Free University Berlin; 1999 [76] Sanad RA, AbdelMalak NS, Badawi AA Formulation of a novel oxybenzoneloaded nanostructured lipid carriers (NLCs) Aaps Pharmscitech 2010;11 (4):1684–94 [77] Kaur S, Nautyal U, Singh R, Singh S, Devi A Nanostructure Lipid Carrier (NLC): the new generation of lipid nanoparticles Asian Pac J Health Sci 2015;2 (2):76–93 [78] Xia Q, Saupe A, Müller RH, Souto EB Nanostructured lipid carriers as novel carrier for sunscreen formulations Int J Cosmet Sci 2007;29(6):473–82 [79] Müller-Goymann CC Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001 12 [80] [81] [82] [83] [84] [85] [86] [87] [88] [89] [90] P Jain et al / Egyptian Journal of Basic and Applied Sciences xxx (2017) xxx–xxx nanoparticles for topical administration Eur J Pharm Biopharm 2004;58 (2):343–56 Pardeike J, Hommoss A, Müller RH Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products Int J Pharm 2009;366(1):170–84 Severino P, Santana MH, Souto EB Optimizing SLN and NLC by 2 full factorial design: Effect of homogenization technique Mater Sci Eng C 2012;32 (6):1375–9 Weiss J, Gaysinsky S, Davidson M, McClements J Nanostructured encapsulation systems food antimicrobials Global Issues Food Sci Technol 2009:1 Wissing SA, Kayser O, Müller RH Solid lipid nanoparticles for parenteral drug delivery Adv Drug Deliv Rev 2004;56(9):1257–72 Porter CJ, Trevaskis NL, Charman WN Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs Nat Rev Drug Discov 2007;6 (3):231–48 Gramdorf S, Hermann S, Hentschel A, Schrader K, Müller RH, KumpugdeeVollrath M, Kraume M Crystallized miniemulsions: Influence of operating parameters during high-pressure homogenization on size and shape of particles Colloids Surf A 2008;331(1):108–13 Souto EB, Müller RH SLN and NLC for topical delivery of ketoconazole J Microencapsul 2005;22(5):501–10 Araújo J, Nikolic S, Egea MA, Souto EB, Garcia ML Nanostructured lipid carriers for triamcinolone acetonide delivery to the posterior segment of the eye Colloids Surf B Biointerfaces 2011;88(1):150–7 Lopez-Huertas E Health effects of oleic acid and long chain omega-3 fatty acids (EPA and DHA) enriched milks A review of intervention studies Pharmacol Res 2010;61(3):200–7 Nawar WW Lipids In: Fennema OR, editor Food chemistry New York: Marcel Dekker; 1996 p 225–319 Severino P, Pinho SC, Souto EB, Santana MH Polymorphism, crystallinity and hydrophilic–lipophilic balance of stearic acid and stearic acid–capric/caprylic [91] [92] [93] [94] [95] [96] [97] [98] [99] [100] triglyceride matrices for production of stable nanoparticles Colloids Surf B 2011;86(1):125–30 Esposito E, Mariani P, Ravani L, Contado C, Volta M, Bido S, Drechsler M, Mazzoni S, Menegatti E, Morari M, Cortesi R Nanoparticulate lipid dispersions for bromocriptine delivery: characterization and in vivo study Eur J Pharm Biopharm 2012;80(2):306–14 Fathi M, Varshosaz J, Mohebbi M, Shahidi F Hesperetin-loaded solid lipid nanoparticles and nanostructure lipid carriers for food fortification: preparation, characterization, and modeling Food Bioprocess Technol 2013;6(6):1464–75 Hentschel A, Gramdorf S, Müller RH, Kurz T Β-Carotene-loaded nanostructured lipid carriers J Food Sci 2008;73(2):N1–6 Williams PA Food emulsions: principles, practice, and techniques Int J Food Sci Technol 2001;36(2):223–4 Klang V, Matsko NB, Valenta C, Hofer F Electron microscopy of nanoemulsions: an essential tool for characterization and stability assessment Micron 2012;43(2):85–103 Kumbhar DD, Pokharkar VB Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: physicochemical investigations Colloids Surf A 2013;416:32–42 Mäder K, Mehnert W 1—solid lipid nanoparticles—concepts, procedures, and physicochemical aspects In: Lipospheres in drug targets and delivery: approaches, methods, and applications CRC Press; 2004 p 1–22 Shah NV, Seth AK, Balaraman R, Aundhia CJ, Maheshwari RA, Parmar GR Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study J Adv Res 2016;7(3):423–34 Wang W, Chen L, Huang X, Shao A Preparation and characterization of minoxidil loaded nanostructured lipid carriers AAPS PharmSciTech 2016;27:1–8 Poonia N, Kharb R, Lather V, Pandita D Nanostructured lipid carriers: versatile oral delivery vehicle Future Sci OA 2016;2(3):FSO135 Please cite this article in press as: Jain P et al Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects Egyp Jour Bas App Sci (2017), http://dx.doi.org/10.1016/j.ejbas.2017.02.001