Targeted drug delivery systems By Vishnu Datta M

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Introduction Advantages and disadvantages Basic biological process and events in Targeted delivery

Text of Targeted drug delivery systems By Vishnu Datta M

  • 1. Targeted Drug DeliverySystems

2. ONTARGETTARGETED DRUG DELIVERY SYSTEMSVishnu Datta MDept. of pharmaceuticsJSSCP, MYSOREJSS University 3. ONTARGET Biological processes and events involvedin drug targeting2Agenda Concept. Introduction Advantages and DisadvantagesTargeted Drug delivery 4. ONTARGETIntroduction It is a special form of drug delivery systemwhere the pharmacologically active agent ormedicament is selectively targeted ordelivered only to its site of action orabsorption and not to the non-target organsor tissues or cells. The drug may be delivered: To the capillary bed of the active sites, To the specific type of cell (or) even anintracellular region. Ex- tumour cells but notto normal cells, To a specific organ (or) tissues by complexingwith the carrier that recognizes the target 5. ONTARGETSMART DRUG THERAPY???INDEED1.. 6. ONTARGETReasons for Site specific delivery ofdrugs2Pharmaceutical Drug instability in conventional dosage form SolubilityBiopharmaceutical Low absorption High-membrane bounding Biological instabilityPharmacokinetic / Pharmacodynamic Short half-life Large volume of distribution Low specificityClinical Low therapeutic index. 7. ONTARGETOBJECTIVES To achieve a desired pharmacologicalresponse at a selected sites withoutundesirable interaction at other sites, thereby the drug have a specific action withminimum side effects & better therapeuticindex. Ex- in cancer chemotherapy and in enzymereplacement therapy. 8. ONTARGETIDEAL CHARACTERISTICSTargeted drug delivery system should be-HOW?? Biochemically inert (non-toxic) Non-immunogenic. Both physically and chemically stable in vivoand in vitro. Restrict drug distribution to target cells ortissues or organs Should have uniform capillary distribution. Controllable and predicate rate of drugrelease. 9. ONTARGETIDEAL CHARACTERISTICS Drug release does not effect the drugaction. Therapeutic amount of drug release. Minimal drug leakage during transit. Carriers used must be bio-degradable orreadily eliminated from the body withoutany problem and no carrier inducedmodulation of diseased state. The preparation of the delivery systemshould be easy or reasonably simple,reproductive and cost effective. 10. ONTARGETADVANTAGESControl of drug delivery onto a particular site orvicinity with predeterminedor expected releasekineticsDISADVANTAGES Expensive Technical skill required Stability issues bothChemical and physical biological aswell Yield comparatively very lessAdvantages and DisadvantagesTargeted drug delivery systems 11. ONTARGET 12. ONTARGETBiological processes and eventsinvolved in drug targeting2 Cellular Uptake and Processing Transport across the epithelialbarrier Extravasation Lymphatic Uptake 13. ONTARGETCellular Uptake and Processing Following administration low molar massdrugs can enter into or pass through variouscells by simple diffusion process. Targeted drug delivery usually have macromolecular assemblies hence cannot enter bysuch simple process. Hence take up by aprocess called ENDOCYTOSIS Steps involved : Internalization of the plasma membrane Concomitant with engulfment ofextracellular material 14. ONTARGETCellular Uptake and Processing Phagocytes^^^^ rest of the cells opsosins immunoglobulin G complement C3b fibronectin dysopsonins IgA & sIgA impart degree of hydrophilicity>>>decrease the uptake 15. ONTARGETCellular Uptake and Processing Compared with phagocytosis pinocytosis is auniversal phenomenon in all the cellspinocytosis does not require any externalstimulus Pinocytosis is divided into two types: Fluid phases pinocytosis Adsorptive pinocytosis Compared with phagocytosis fluid phasepinocytic capture of molecules is relativelyslower being directly proportional to theconcentration and size dependant 16. ONTARGETTransport across the epithelialbarrier The oral buccal nasal vaginal and rectalcavities are internally lined with one ormore layers of epithelial cells Depending on the position and function inthe body epithelial cells can be varied formsThree layer physiology: Epithelial Lamia propria Basal lamina Low molar mass drugs cross the above bypassive difussion carrier mediated systemsans selective and non-selective endocytosis 17. ONTARGETTransport across the epithelialbarrier The polar materials diffuse through tightjunctions of epithelial cells Passive transport is usually higher indamaged mucosa where as active transportdepends on structural integrity of epithelialcells Positively charged particles showedincreased uptake than negatively chargedcounterparts. Absoption of drugs from buccal viatranscellular and paracellular later beingdominant 18. ONTARGETTransport across the epithelialbarrier Some proposals Ex-vaginal cavity could be an effectivedelivery site for certain pharmaceuticals Such as calcitonin for the treatment ofpostmenopausal osteoporosis It was demonstrated that when deliveredvaginally first undergo uterine pass effectsuggesting that the vaginal route can beuseed to target to the uterus 19. ONTARGETExtravasation Many diseases result from the dysfunction ofcells located outside the cardiovascularsystem thus for a drug to exert itstherapeutic effects it must exit from thecentral circulation this process of transvascular exchange is called Extravasationwhich is governed by blood capillary walls Factors that control permeability ofcapillaries Structure of the capillary wall Pathological condition Rate of blood and lymph supply Physicochemical factors of drug 20. ONTARGETExtravasation The structure of the blood capillary varies indifferent organs tissues. It consists of a single layer of endothelialcells joined together by intercellularjuctions Depending on the morphology and continuityof the endothelial layer and the basementmembrane blood capillaries are divided into Continuous Fenestraded Sinusoidal 21. ONTARGETExtravasation 22. ONTARGETExtravasation Continuous capillaries are common andwidely distributed in the body exhibit tightinter endothelial junctions and anuninterrupted basement membrane Fenestrated capillaries shows inter-endothelial gaps of 20-80nm Sinusoidal capillaries show inter endothelialgaps of 150nm Depending on the tissue or organ the basalmembrane is either absent ex-liver orpresent in discontinuous ex-spleen and bonemarrow 23. ONTARGETExtravasation Macromolecules can transverse the normalendothelium by passive process such asnonspecific fluid phase trans capillarypinocytosis and passage through interendothelial junctions gaps or fenestrate orby receptor-mediated transport systems Organs such as the lung with very largesurface areas have a proportionately largetotal permeability and consequently a highextravasation Depends on charge shape, size, HLB,characteristics of macromolecules 24. ONTARGETExtravasation The endothelium of brain is the strongest ofall endothelia formed by continousnonfenestrated endothelial cells which showno pinocytic activity Soluble macromolecules permeate theendothelial barrier more readily thanparticulate macromolecules the rate ofmovement of fluid across the endotheliumappears to be directly related to the diffbetween the hydrostatic and osmotic forces 25. ONTARGETLymphatic Uptake Following extravasation drug molecules caneither reabsorb into the blood streamdirectly or enter into the lymphatic systemand return with the lymph to the bloodcirculation Also drugs administered by subcutaneousintracellular transdermal peritoneal routescan reach the systemic circulation bylymphatic system 26. ONTARGETLymphatic Uptake 27. ONTARGETLymphatic Uptake Factors know to influence the clearance ofdrugs from interstitial sites Route of administration Size and surface characteristics of particles Formulation medium The composition and pH of the interstitial fluid and Disease within the interstitium The direct delivery of drugs into lymphaticshas been proposed as a potential approachto kill malignant lymphoid cells located inlymph nodes 28. ONTARGETReferences:1. Muller, R; Keck, C (2004). "Challenges and solutionsfor the delivery of biotech drugs a review of drugnanocrystal technology and lipidnanoparticles". Journal of Biotechnology 113 (13):151170. doi:10.1016/j.jbiotec.2004.06.0072. Target-Oriented Drug Delivery Systems(9) by Vijaykumar Modern Pharmaceutics Volume 2Applications and Advances; Fifth edition edited byAlexander T. Florence 329-342.3. Encyclopaedia of controlled delivery by EdithMathiowitz4. S.P Yyas and R.K Khar Controlled drug Deliveryconcepts and advances Vallabh prakashan firstedition 29. ONTARGET~~~Thank you~~~