Đây là bài giảng về hoá học các hệ dẫn truyền thuốc dành cho các lớp cao học của Dr. Le Thanh Dung, bài giảng được trình bày bằng tiếng Anh giúp các bạn tiếp cận với cách trình bày bằng tiếng anh trong các bài báo cáo khoa học của mình, bài rất hay.
THE CHEMISTRY OF DRUG DELIVERY SYSTEMS Dr Lê Thành Dũng Org Chem Eng Group Faculty of Chemical Engineering Tel: 38647256 ext 5681 Email: ltdung@hcmut.edu.vn OBJECTIVES On the completion of this course, the student should be able to have a deep understanding of the chemical aspects of drug delivery systems that have recently attracted attention from the chemistry and chemical engineering community EVALUATION Seminar: 70% Students have to work in group for the preparation and the presentation of their seminar subject Evaluation will be given based on individual contribution (preparation, discussion), the oral presentation and the answers to the questions Final exam: 30% Students will receive a publication on drug delivery system at least one week before the day of the exam The exam questions will be based on the given article REFERENCES Martin Malmsten, Surfactants and polymers in drug delivery, Marcel Dekker, New York, 2002 Glen S Kwon, Polymeric drug delivery systems, Taylor & Francis Group, New York, 2005 Ram B Gupta, Uday B Kompella, Nanoparticle technology for drug delivery, Taylor & Francis Group, New York, 2006 Publications in Elsevier, Royal Society of Chemistry, American Chemical Society, Wiley InterScience journals… CONTENTS Generalities of drug delivery Liposomes as drug delivery systems Polymers and polymeric systems for drug delivery Dendrimers for drug delivery GENERALITIES OF DRUG DELIVERY DRUG DELIVERY SYSTEM Definition: A drug delivery system is a formulation or a device that safely brings a therapeutic agent to a specific body site at a certain rate to achive an effective concentration at the site of drug action Roles: Carry Transport Protect Distribute Enhance body retention, the efficacy of the treatment ROUTES OF DRUG ADMINISTRATION Topical delivery ORAL DELIVERY (GASTROINTESTINAL ADMINISTRATION) ORAL DELIVERY (GASTROINTESTINAL ADMINISTRATION) Advantages: safest most convenient most economical Disadvantages: poorly absorption of large, highly charged molecules degradation of drug by stomach acid, various enzymes in the GI tract DRUG RELEASE MECHANISMS – DIFFUSION CONTROLLED Passive diffusion of drug across hydrogel membranes can be described by the Fick’s first law x J x = D k D= J dC k dx kBT 6R (Stokes-Einstein equation) x : Flux of species k along x - direction k D: diffusion coefficient C: concentration J depends on the mesh sizes of swollen hydrogels (5-100 nm) CONTROLLED-RELEASE HYDROGEL SYSTEMS Time-controlled systems E.g copolymeric hydrogel disks for controlled release of burenorphine (treating opioid dependence) by buccal route Stimuli-induced release systems STIMULI-INDUCED RELEASE SYSTEMS Brannon-Peppas, MPB, 1997, 11, 34 pH-RESPONSIVE HYDROGELS pH-RESPONSIVE HYDROGELS PAA PDEAEMA TEMPERATURE-RESPONSIVE HYDROGELS Bromberg et al Adv Drug Deliv Rev 1998, 31, 197 DENDRIMERS FOR DRUG DELIVERY STRUCTURE OF DENDRIMERS periphery Branch point core 2D 4th generation 3D cavity Generation: same external functional groups as starting molecule SYNTHESIS OF DENDRIMERS Divergent synthesis: 1st generation Coupling Activation Coupling Activation 2nd generation SYNTHESIS OF DENDRIMERS Divergent synthesis – the first dendrimer: 1st generation 2nd generation Vögtle F et al Synthesis 1978, 155 De Brabander E.M.M et al Angew Chem Int Ed Engl 1993, 32, 1308 SYNTHESIS OF DENDRIMERS Divergent synthesis – PAMAM (PolyAMidoAMine): Tomalia D A et al Macromolecules 1986, 19, 2466 Tomalia D A US Pat 4507466, 1985, Amine & ester terminated poly(amidodamine) dendrimers SYNTHESIS OF DENDRIMERS Convergent synthesis: Dendron Dendrimer Core SYNTHESIS OF DENDRIMERS Convergent synthesis – preparation of dendrons: Coupling Activation 1st generation Coupling 2nd generation SYNTHESIS OF DENDRIMERS Convergent synthesis – Fréchet-type dendrons (polyaryl ethers): Bn: Benzyl [G-1]-OH [G-1]-Br [G-3]-Br [G-2]-Br Fréchet et al J Am Chem Soc 1990, 112, 7638 Chem Commun 1990, 1010 SYNTHESIS OF DENDRIMERS Comparison between divergent & convergent synthesis: Divergent construction Core Convergent construction 1/3 eq eq 1/3 eq 12 eq Terminal site for monomer connectivity Focal site for monomer connectivity 1/4 eq 36 eq Branch juncture Void volume Core Peripheral region ... On the completion of this course, the student should be able to have a deep understanding of the chemical aspects of drug delivery systems that have recently attracted attention from the chemistry. .. Society of Chemistry, American Chemical Society, Wiley InterScience journals… CONTENTS Generalities of drug delivery Liposomes as drug delivery systems Polymers and polymeric systems for drug delivery. .. Targeted drug delivery systems: deliver drug to a desired body location, organ, tissue, specific cells… Controlled-release drug delivery systems: preprogramed drug release By the route of delivery: