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Drug Delivery System 藥物投遞系統

Drug Delivery System 藥物投遞系統. 生科系 04 級 黃玫璇 891672 生科系 04 級 許哲源 891659 生科系 04 級 蕭宏展 891631 生科系 04 級 楊淳竣 891625. 藥物釋控系統. 黃玫璇 891672. 藥物釋控系統. 1. 何謂藥物釋控 2. 發展釋控的優點 3. 藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlled. 藥物釋控系統.

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Drug Delivery System 藥物投遞系統

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  1. Drug Delivery System藥物投遞系統 生科系04級 黃玫璇 891672 生科系04級 許哲源 891659 生科系04級 蕭宏展 891631 生科系04級 楊淳竣 891625

  2. 藥物釋控系統 黃玫璇 891672

  3. 藥物釋控系統 1.何謂藥物釋控 2.發展釋控的優點 3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlled

  4. 藥物釋控系統 1.何謂藥物釋控 2.發展釋控的優點 3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlled

  5. 【藥物釋控】：Drug Controlled Release System 將藥物以特殊的化學包覆，讓藥物在某一種狀態(如PH值改變)下適時(ex:延長)適量釋出。 這種控釋劑型的技術發展，目前廣泛地應用於一般的製藥化學工業中。

  6. 藥物釋控系統 1.何謂藥物釋控 2.發展釋控的優點 3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlled

  7. Potential Advantages of • Controlled Release Systems • maintenance of drugs at therapeutically desirable levels • 2. the ability to localize drugs to target organs to minimize systemic effects • 3. improved patient compliance • 4. protection from degradation for drugs with short in vivo lifetimes.

  8. Side Effects Therapeutic Dose Desired Range Controlled Release vs. Single Dose

  9. 藥物釋控系統 1.何謂藥物釋控 2.發展釋控的優點 3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlled

  10. Types of Controlled Release Devices 【 Diffusion controlled】 Diffusion through membrane or bulk polymer 【 Chemically controlled】 ˙ polymer erosion： surface erosion, bulk erosion ( combination of erosion and diffusion ) ˙ pendent chain 【 Solvent-activated controlled】 ˙ osmotic transport of water through semi permeable membrane ˙ water penetration into glassy polymer

  11. 1.Diffusion controlled 【 Stomach/Intestine – Liquid】 【 Capsule edge – Gel 】 • Biocompatible polymer 【 Capsule center – Dry 】 • Allows for delayed release △release rates are determined by polymer property and partition coefficient of the drug to be released. △advantage ˙ drug diffuses out of matrix at defined rate △disadvantage ˙ efficiency of diffusion of large molecules ˙ danger of ‘dose dumping’ in barrier systems

  12. 2.Chemically controlled ˙ erosion： Surface erosion, Bulk erosion △ capsule is eroded by the acids in the stomach △ advantage ˙ inject able (micro spheres) ˙ biodegradable (need not be removed surgically) △ disadvantage ˙ difficult to stop once injected

  13. 2.Chemically controlled ˙ pendent chain △ drug is covalently bound to the polymer and is released by bond scission owing to water or enzymes

  14. 3. Solvent-activated controlled △ the active agent is dissolved or dispersed within a polymeric matrix and is not able to diffuse through that matrix. △ advantage ˙ complex control △ disadvantage ˙ generally more bulky devices and require implantation

  15. Biodegradable Polymers

  16. Application

  17. Targeting moiety for cell 891659 許哲源

  18. Introduction • For the past several decades, researchers and clinicians have been using drugs and radiation to kill tumor cells. • The chemotherapy and radiotherapy are only semiselective for malignant cells. • In contrast, targeting drug therapy has the potential for greater specificity. • With the advent of monoclonal antibody (MoAb) technology, researcher have been able to target different agents to target cells more effectively. Pharmacol. Ther. 1994, 64:127–54

  19. EPR effect • The Enhanced Permeability and Retention effect in tumor tissue • Tumor cells show a higher degree of uptake of macromolecules by endocytosis than normal cell. Microvasc. Res. 1996, 51:327-346

  20. Introduction • Immunotoxins (Its) contain a targeting moiety for delivery and a toxic moiety for cytotoxicity. • The toxins ( plant or bacterial toxin) are catalytic, fewer than 10 molecules in the cytosol of a target cell enough to be lethal. Pharmacol. Ther. 1994, 63(3):209–234

  21. Schematic presentation of ligand-containing, shielded DNA complexes for tumor-targeted gene transfer Journal of Controlled Release 2003, 91:173-181

  22. Targeting Moiety • The targeting agents currently used to construct ITs are MoAbs, growth factors/cytokines, and soluble receptors. • MoAbs are the most frequently used. J. Clin. Immunol. 1992, 12:391–405

  23. Targeting Moiety

  24. Targeting Moiety • Bispecific antibodies are novel targeting agents constructed by linking either chemically or genetically two different Fab fragment, one arm of which is directed against a target cell and the other against effector T cells or NK cells (e.g. anti-CD22/anti-CD3-RTA). Blood 1993, 82:2224–34

  25. Toxin Moiety • The most commonly used toxic moieties are derived from either bacteria[e.g. Pseudomonas exotoxin(PE) or diptheria toxin(DT)], or plants(e.g. abrin or ricin).

  26. Toxin Moiety • Both types of toxins kill cells by inhibiting protein synthesis. • Plant toxins damage 28S rRNA, • Bacterial toxins inactivate EF-2 Ann. Rev. Immunol. 1996. 14:49–71

  27. Linkers • For in vivo therapy, the toxic moiety of the IT must be coupled to the targeting ligand so that it remains stable in the blood and tissues but is separated from the targeting domain for effective translocation into the cytoplasm.

  28. Factors affecting the potency of an IT • Binding affinity of the targeting moiety • The density of the target Ag on the cell • Naturally internalized or induced to do so. • Intracellular routing • May promote proliferation of target cell population

  29. Clinical trials • The field of immnotoxin therapy is in its infancy. To date most ITs are just entering Phase II/III trials. • Anti-IT antibodies were generated in most trials

  30. Conclusions • For the therapy of cancer, ITs have yielded higher response rates in Phase I/II trials than some of the drugs used today. • The generation of new constructs, combinatorial therapy, and in the case of cancer therapy, treatment of tumors that are amenable to IT-mediated killing will eventually result in effective treatment protocols.

  31. References • Thrush GR., Lark LR., Clinchy BC., and Vitetta ES. Immunotoxins: An update. Ann. Rev. Immunol. 14: 49-71. 1996. • Rustamzadeh E., Low WC., Vallera DA., and Hall WA. Immunotoxin therapy for CNS tumor. Journal of Neuro-oncology. 64: 101-116. 2003. • Houshmand P., and Zlotnik A. Targeting tumor cells. Current Opinion in Cell Biology. 15: 640-644. 2003 • Ogris M., Walker G., Blessing T., Kircheis R., Wolschek M., and Wagner E. Tumor-targeted gene therapy: strategies for the preparation of ligand-polyethylene glycol-polyethylenimine/DNA complexes. Journal of Controlled Release. 91: 173-181. 2003 • Carlsson J., Aronsson EF., Hietala SO., Stigbrand T., and Tennvall J. Tumuor therapy with radionuclides: assessment of progress and problems. Radiotherapy and Oncology. 66: 107-117. 2003.

  32. Overview of Worldwide Drug Market 主講:蕭宏展

  33. Worldwide drug market sales

  34. 2003全球各區域藥品市場銷售額 Total sales: around 5000億美金 資料來源:IMS Health

  35. 全球十大藥物銷售

  36. Drug delivery system market • 2002年 worldwide sales: $41.1 billion • 2007年(e) worldwide sales: $66 billion 資料來源:Front Line Strategic Consulting, Inc.

  37. Drug delivery system

  38. Oral controlled release • Sustained release or extended release drug • Compound is less susceptible to gastric degradation • Company:Elan Corp. and J&J Alza • Product:Nexium (R) Esomeprazole ($3302 millino) 、Losec/Prilosec for treatment of gastric ulcer .

  39. Polymer • A method of drug delivery in which a therapeutic is encapsulated in polymeric matrix and is slowly released at the site of action via diffusion and surface erosion. • Inactive in the bloodstream • Company: J&J Alza 、Atrix • Product: PEG-Intron (pegylated interferon) for treatment of chronic hepatitis C

  40. Pulmonary • Improve patient compliance associated with the relative comfort and convenience of inhalers. • Company: GlaxoSmithKline、Aerogen,Inc.、Nektar therapeutics • Product: Aerodose® Insulin Inhaler、 Seretide/Advair for treatment of asthma

  41. Transdermal • Enable the passage of drug molecules across skin • Lower dosing of medications result in few adverse side effects • Company: J&J Alza 、Noven Pharmaceutical • Product: Catapres-TTS® (clonidine) for treatment of hypertension 、 NicoDerm® CQ® (nicotine) and Clear NicoDerm® CQ®

  42. Transmucosal • Drug is introduced to the body across a mucous membrane which allows for the avoidance of the gastrointestinal tract and first pass liver metabolism and consequently allows the therapeutic to directly enter into circulation. • Company: Nastech Pharmaceutical Co. 、Pherin Pharmaceuticals • Product:Premarin (estrogen) for treatment of symptom of menopause in women. Nasonex for treatment of specific allergy situation

  43. Major drug delivery company stock2004.5.4 資料來源:www.pharmcast.com

  44. ALZA • 1968 ALZA Corporation was founded by Dr. Alejandro Zaffaroni in 1968 to realize his vision of sophisticated pharmaceutical products that precisely control the targeting, timing and dosing of therapeutic compounds.

  45. Products • OROS® Technology (11) • D-TRANS® Transdermal Technology (7) Catapres-TTS® (clonidine), Duragesic® (fentanyl), Estraderm® (estradiol), NicoDerm® (nicotine), Transderm-Nitro® (nitroglycerin) • STEALTH® Liposomal TechnologyDoxil® (doxorubicin) an anti-cancer drug for the treatment of ovarian cancer • DUROS® Implant TechnologyViadur® (leuprolide acetate implant) treatment for prostate cancer

  46. 1995 Pfizer introduces Glucotrol XL®, its second once-daily product using ALZA's OROS® technology. It is introduced as an adjunct to diet for the control of hyperglycemia in patients with non-insulin dependent diabetes. • 2001 ALZA Becomes a Member of the Johnson & Johnson Family of CompaniesALZA continues as a leader in the development and manufacture of pharmaceutical products incorporating its novel, proprietary drug delivery technologies for its partners in the global healthcare industry.

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