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Ho Chi Minh City University of Technology Chemical Engineering Polymeric nanoparticles for oral drug delivery Advisor : Dr Le Thi Hong Nhan Postgraduate Student: Huynh Kim Ngan Nguyen Thi Kim Hang Nguyen Hoai Thuong 4/20/16 Le Thi Bich Phuong ROUTES OF DRUG ADMINISTRATION Oral Drug System Advantages  Safes  Most convenient  Most economical Disadvantages  Poorly absorption of large  Highly charged molecules  Degradation of drug by stomach acid Parenteral Administration Intramuscular    Patient can administer the drug himself Larger volume than subcutaneous By-pass first pass metabolism    Invasive – patient disconfort Irritation, inflamation May require some training Transdermal administration • Advantages Solution for drug that can not be administered by oral delivery Reliability, precision of dosage • Disadvantages Discomfort Possibility of infection Tissue damage Global drug delivery market by administration mode Oral Delivery (Gastrointestinal Administration) Gastrointestinal Administration Gastrointestinal Administration  Saliva? pH = 5.5 –  Oral cavity : water rich environment  selection of hydrophylic matrices as drug carriers Dosage forms  Liquid  Dispersed system  Solids Nanoprecipitation NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Supercritical fluid technology • Two principles have been developed for the production of nanoparticles using supercritical fluids: Rapid expansion of supercritical solution (RESS) Rapid expansion of supercritical solution into liquid solvent (RESOLV) NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Rapid expansion of supercritical solution NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Rapid expansion of supercritical solution into liquid solvent NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Methods for preparation of nanoparticles from polymerization of monomers Emulsion Yashwant Pathak ,Deepak Thassu (2009), Drug delivery nanoparticles formulation and characterization, Volume 191 Mini emulsion A typical formulation used in miniemulsion polymerization consists of water, monomer mixture, costabilizer, surfactant, and initiator Micro emulsion Although emulsion and micro-emulsion polymerization appear similar because both methods can produce colloidal polymer particles of high molar mass, they are entirely different when compared kinetically Ionic gelation or coacervation of hydrophilic polymers NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Enhanced Oral Biovailability Local Delivery –Colon Specific Targeting APPLICATION Lymphatic Targeting Systemic Targeting Enhanced Oral Biovailability  Insulin encapsulated in PBCA nanocapsules reduced glycemia by 50 -60%  The absorption enhancement was explained on the basis of the dual effect of mucoadhesion of NPs Enhanced Oral Biovailability  The relative bioavailability of CyA from chitosan NPs was increased by about 73%, 18% from gelatin NPs  The relative bioavailability of CyA from NPs increased for Eudragits S100, L10055, CyA-L100 NPs Direct contact of the carriers with the inflammation site • Accumulate tin the ulcer, adhere to nonulcerated inflamed tissues • Local Delivery- Colon Specific Targeting • Target the inflamed tissue in tintestinal bowel diseases Lymphatic Targeting  Incorporating the vaccine into the NPs drug delivery system  The vaccine is protected again degradation on its way to the mucosal tissue  Oral administra-tion of vaccines might result in improvements in efficacy Systemic Targeting Uptake from the intestine NPs can appear in the systemic circulation Deliver drugs in virtually any organ perfused by blood Future Directions Drug or human use should be safe, efficacious, and of an acceptable quality The safety of NPs has to be established not only for drug but also for the matrixused for preparing the NPs [...]...Controlled Release Targeted Delivery Nanoparticle for Drug Delivery System Polynmeric Drug delivery system Prodrug Prodrug Prodrug = Drug + Drug delivery system Types of Prodrugs Comparison oral drug delivery and oral nanoparticles delivery 4/20/16 18 6 5 4 • Dosage Form 3 • Dose 2 • Drug Release 1 • • Freeze-Drying Nanoparticle formulation Stabilizers for NPs... Natural polymers 4/20/16 Synthetic polymers 19 Natural polymers Advantages - Low cost - Biocompatibility - Aqueous solubility Disadvantages - The presence of impurities - Batch-to-batch varibility - Low hydrophobicity 4/20/16 20 Synthetic polymers Advantages - More reproducible - Degradation rates - Molecular weights - Copolymer compositions Disadvantages - Limited solubility - Soluble only in organic solvents... 4/20/16 29 PRODUCTION OF POLYMERIC NANOPARTICLES Depend on • • • • The nature of the polymer employed The nature of the drug to be encapsulated Intended use of the system Intended duration of the therapy Ex Chitosan PRODUCTION OF POLYMERIC NANOPARTICLES Devasier Bennet and Sanghyo Kim (2014), Polymer nanoparticles for Smart Drug Delivery, chapter 8 Methods for preparation of nanoparticles from dispersion... DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Dialysis NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) Nanoprecipitation NAGAVARMA B V N, HEMANT K.S.YADAV*,... Natural polymers are formed in nature during the growth cycles of all organisms Proteins Natural polymers Collagen Agarose Albumin Alginate Gelatin Carraheenan Polysaccharides Hyaluronic acid Dextran Chitosan 4/20/16 Cyclodextrins 22 Synthetic polymers Poly(lactic acid) (PLA) Polyesters Poly(glycolic acid) (PGA) Poly(hydroxy butyrate) Synthetic polymers Polycaprolactone (PCL) Polyanhydrides Poly(adipic... of nanoparticles from dispersion of preformed polymer Solvent Evaporation Yashwant Pathak ,Deepak Thassu (2009), Drug delivery nanoparticles formulation and characterization, Volume 191 Emulsification /Solvent Diffusion Yashwant Pathak ,Deepak Thassu (2009), Drug delivery nanoparticles formulation and characterization, Volume 191 Salting Out Salting out is based on the separation of a water miscible... Miscellaneous  Stearic acid and Gliadins Hydroxypropyl methyl cellulose phthalate NPs are also prepared by utilizing simple organic or inorganic compounds 4/20/16 24 Stabilizers for NPs Stabilizers are used to prevent the aggregation of particles by conferring a surface charge  The higher the surface charge the greater is the stability 4/20/16 25 Freeze-Drying  Ensuring stability  Ease in storage... Asian Journal of Pharmaceutical and Clinical Research (2012) Nanoprecipitation NAGAVARMA B V N, HEMANT K.S.YADAV*, AYAZ A, VASUDHA L.S, SHIVAKUMAR H.G, DIFFERENT TECHNIQUES FOR PREPARATION OF POLYMERIC NANOPARTICLES- A REVIEW, Asian Journal of Pharmaceutical and Clinical Research (2012) ... Advantages - Low cost - Biocompatibility - Aqueous solubility Disadvantages - The presence of impurities - Batch-to-batch varibility - Low hydrophobicity 4/20/16 20 Synthetic polymers Advantages - More... Synthetic polymers Advantages - More reproducible - Degradation rates - Molecular weights - Copolymer compositions Disadvantages - Limited solubility - Soluble only in organic solvents 4/20/16 21... Eudragits S100, L10055, CyA-L100 NPs Direct contact of the carriers with the inflammation site • Accumulate tin the ulcer, adhere to nonulcerated inflamed tissues • Local Delivery- Colon Specific Targeting