Gr meet-04-10-2006
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This document discusses pulmonary alveolar drug delivery. The lung is an effective drug delivery route as it has a large surface area and requires small drug amounts. Drugs can be delivered via aerosols, powders, or solutions to treat respiratory diseases or deliver drugs systemically. The alveolar epithelium contains type I and II cells and presents a barrier to drug absorption. Various drug delivery systems target the lung including liposomes, nanoparticles, and exogenous surfactants. Pulmonary delivery is a promising non-invasive alternative to injection for macromolecules like peptides, proteins, genes, and vaccines.
Gr meet-04-10-2006
- 1. Pulmonary Alveolar DrugPulmonary Alveolar Drug DeliveryDelivery Samares C Biswas Oregon Health & Science University, Portland, OR 97239, USA
- 2. Purposes of Different Drug DeliveryPurposes of Different Drug Delivery Systems and RoutesSystems and Routes Drugs • deliver effectively in the right place • Produce no toxic effects • produce therapeutic benefit • increase drug bioavailability • increase the fraction of the drug accumulated in the required zone • and more
- 3. Drug Delivery RoutesDrug Delivery Routes • Parenteral routes (intravenous,Parenteral routes (intravenous, intramuscular, subcutaneous)intramuscular, subcutaneous) • Trans-tissue and local delivery • Oral/GIT drug delivery (gastro intestinal track) • Transdermal drug delivery (Skin) • Ocular drug delivery (Eye) • Nasal Drug Delivery (Nose) • Otic Drug Delivery (Ear) • Pulmonary Drug Delivery (Lung) AE, absorption enhancers and/or EI enzyme inhibitors via some routes (eg nasal); EP, electroporation/iontophoresis (specific for dermaldelivery); RT, respiratory tract
- 4. Lung as an Effective Drug Delivery RouteLung as an Effective Drug Delivery Route Pulmonary drug delivery • Large surface area • Requires very small amount of drug Local targeting for the treatment of respiratory diseases and a viable option for the delivery of drugs systemically – protein and peptide – Growth hormones – gene therapy (e.g. in the treatment of cystic fibrosis) – Vaccines
- 6. Lung Alveolar EpitheliumLung Alveolar Epithelium • Two specialized epithelial cell – the terminally differentiated squamous alveolar epithelial type-I (ATI) cell constitutes approximately 93 per cent of the alveolar epithelial surface area (33 per cent of alveolar epithelial cells by number) – the surfactant producing cuboidal alveolar epithelial type- II (ATII) cell comprising the remaining 7 per cent by surface area and 67 per cent by epithelial cell number
- 7. Schematic Diagram of the Varying MucosalSchematic Diagram of the Varying Mucosal Barriers within the LungBarriers within the Lung EP: epithelial layer; BM: basement membrane; SM: smooth layer; FC: fibrous coat
- 8. Electron Micrograph of the AlveolarElectron Micrograph of the Alveolar -Capillary Barrier in the Lung-Capillary Barrier in the Lung AS = alveolar airspace C = capillary lumen TJ = Tight Junction • Capillary microvascular endothelial (CME) cells • Alveolar type I epithelial (ATI) cells Free cytosolic vesicles Flask- shapes Caveolae
- 9. Barriers in Pulmonary Drug absorptionBarriers in Pulmonary Drug absorption • Lipid monolayer • Alveolar Epithalium – Type-I Cells (Cover 96% Area) – Type-II Cells (Cover 3% Area) – Phagocytics Macrophages (take part in defence mechanisms) • Enzymes (less proteolytics enzymes than other organs)
- 10. Epithelial Drug Transport MechanismsEpithelial Drug Transport Mechanisms
- 11. Drug Prodrug Biological barrier Parent Drug Prodrug Transporter Carrier- Mediated transport Biotransformation Passive diffusion Transporter Targeted Drug deliveryTransporter Targeted Drug delivery
- 12. Drug Delivery SystemsDrug Delivery Systems
- 13. Pulmonary Drug Delivery SystemsPulmonary Drug Delivery Systems Pulmonary delivery is effected in a variety of ways • aerosols (metered dose inhaler systems,MDIs) • powders (dry powder inhalers, DPIs) • solutions (nebulizers) All of these drugs contain nanostructures such as liposomes, micelles, nanoparticles and dendrimers. Aerosol products for pulmonary delivery comprise more than 30% of the global drug delivery market.
- 14. Exogenous Surfactant as Drug Delivery SystemsExogenous Surfactant as Drug Delivery Systems • Solubility of drugs in lipidsSolubility of drugs in lipids • Effects of drug on the interfacial properties ofEffects of drug on the interfacial properties of lung surfactantlung surfactant • Activity of the drug in the presence ofActivity of the drug in the presence of surfactantsurfactant • Delivering capability in the Epithelial cellsDelivering capability in the Epithelial cells Non-polar drugs are ideal for this drug deliveryNon-polar drugs are ideal for this drug delivery systemsystem
- 15. Anatomy of the Human LungAnatomy of the Human Lung
- 16. Clinical and Potential Routes of AdministrationClinical and Potential Routes of Administration for Therapeutic Peptides and Proteinsfor Therapeutic Peptides and Proteins without absorption enhancers (AE) and/or enzyme inhibitors (EI) via some routes (eg nasal); EP, electroporation/iontophoresis (specific for dermaldelivery); RT, respiratory tract.
- 17. The Pulmonary Drug Delivery RouteThe Pulmonary Drug Delivery Route A promising alternative to injection for the delivery of macromolecules • peptides • proteins • Gene • vaccines