Targeted Drug Delivery Systems

‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’

1. TargetedDrugDelivery Systems
By
SURYAKANT VERMA
Assistant Professor,
Department ofPharmaceutics,

2. ONTARGET
Concept.Introduction
AdvantagesandDisadvantages
Biologicalprocessesand eventsinvolved indrug
targeting
.
Agenda
TargetedDrugdelivery

3. ONTARGET
•Itisaspecialformofdrug deliverysystem wherethe
pharmacologicallyactiveagentor medicamentis
selectivelytargetedor deliveredonlytoitssiteofaction
or absorptionandnottothe non-targetorgans ortissues
or cells.
•Thedrugmaybe delivered:
Tothecapillarybedof the active sites,
Tothespecifictypeof cell(or)evenan intracellular
region.Ex-tumourcellsbutnot tonormal cells,
Toa specificorgan (or)tissuesbycomplexing withthe
carrierthatrecognizesthetarget
Introduction

4. •Itisamethodofdeliveringmedicationtoapatientina
mannerthatincreasestheconcentrationofthemedication
insomepartsofthebodyrelativetoothers.
•Targeteddrugdeliveryseekstoconcentratethemedication
inthetissuesofinterestwhilereducingtherelative
concentrationofthemedicationintheremainingtissues.
•Thisimprovesefficacyandreducesideeffects.
‘Targeteddrugdeliverysystemisaspecialformofdrugdelivery
systemwherethemedicament isselectivelytargetedor
deliveredonlytoitssiteofactionorabsorptionandnottothe
non-targetorgansortissuesorcells.’

5. ONTARGET
SMARTDRUGTHERAPY???
INDEED..

6. ONTARGET
Reasons for Site specific delivery of drugs
Pharmaceutical
Druginstabilityinconventionaldosageform
Solubility
Biopharmaceutical
Lowabsorption
High-membranebounding
Biologicalinstability
Pharmacokinetic/Pharmacodynamic
Shorthalf-life
Largevolumeofdistribution
Lowspecificity
Clinical
Lowtherapeuticindex.

7. ONTARGET
Toachieveadesiredpharmacologicalresponse
ataselectedsiteswithoutundesirableinteraction
atothersites,therebythedrughaveaspecific
actionwithminimumsideeffects&better
therapeuticindex.
Ex-incancerchemotherapyandinenzyme
replacementtherapy.
OBJECTIVES

8. ONTARGET
Targeteddrug deliverysystemshouldbe-
HOW??
•Biochemicallyinert(non-toxic)
•Non-immunogenic.
•Bothphysicallyandchemicallystableinvivoandin
vitro.
•Restrictdrugdistributiontotargetcellsortissuesor
organs
•Should haveuniformcapillarydistribution.
•Controllableandpredicaterate ofdrug release.
IDEALCHARACTERISTICS

9. ONTARGET
•Drugreleasedoesnoteffectthedrugaction.
•Therapeuticamountofdrugrelease.
•Minimaldrugleakageduringtransit.
•Carriersusedmustbebio-degradableorreadily
eliminatedfromthebodywithoutanyproblemand
nocarrierinducedmodulationofdiseasedstate.
•Thepreparationofthedeliverysystemshouldbe
easyorreasonablysimple,reproductiveand
costeffective.
IDEALCHARACTERISTICS

10. ONTARGET
ADVANTAGES
•Controlofdrugdeliveryontoaparticularsiteor
vicinitywithpredeterminedorexpectedrelease
kinetics.
•Drugadministrationprotocolsmaybesimplified.
•Toxicityisreducedbydeliveringadrugtoits
targetsite,therebyreducingharmfulsystemic
effects.
•Drugcanbeadministeredinasmallerdoseto
producethedesireeffect.
•Avoidanceofhepaticfirstpassmetabolism.
•Enhancementoftheabsorptionoftarget
moleculessuchaspeptidesandparticulates.
•Doseislesscomparedtoconventionaldrug
deliverysystem.
•Nopeakandvalleyplasmaconcentration.
•Selectivetargetingtoinfectionscellsthatcompare
tonormalcells.
DISADVANTAGES
•Expensive
•Technicalskillrequired
•Stabilityissuesboth
Chemical and physical
biological as well
•Yieldcomparativelyveryless
AdvantagesandDisadvantages
Targeteddrugdeliverysystems

11. Biologicalprocessesandevents involvedindrug
targeting
•CellularUptakeandProcessing
•Transportacrosstheepithelial barrier
•Extravasation
•LymphaticUptake

13. ONTARGET
CellularUptakeandProcessing
•Followingadministrationlowmolarmassdrugscanenter
intoorpassthroughvariouscellsbysimplediffusion
process.
•Targeteddrugdeliveryusuallyhavemacromolecular
assemblieshencecannotenterbysuchsimpleprocess.
HencetakeupbyaprocesscalledENDOCYTOSIS
•Stepsinvolved:
Internalizationoftheplasmamembrane
Concomitantwithengulfmentofextracellular
material

14. ONTARGET
CellularUptakeandProcessing
•Phagocytes^^^^restofthecellsopsosinsimmunoglobulin GcomplementC3b
fibronectin.
•dysopsoninsIgA&sIgAimpartdegreeofhydrophilicity>>>decreasetheuptake

15. ONTARGET
CellularUptakeandProcessing
•Comparedwithphagocytosispinocytosisisa universal
phenomenonin allthecells pinocytosisdoesnot
requireanyexternal stimulus
•Pinocytosisisdividedintotwotypes:
1.Fluidphasespinocytosis
2.Adsorptive pinocytosis
•Comparedwithphagocytosisfluid phase pinocytic
capture of molecules is relatively slowerbeingdirectly
proportionaltothe concentrationandsizedependant

16. ONTARGET
Transport across the epithelial barrier
•Theoralbuccalnasalvaginalandrectalcavitiesare
internallylinedwithoneormorelayersof
epithelialcells
•Dependingon thepositionandfunctionin thebody
epithelialcells canbevariedforms
Threelayerphysiology:
Epithelial
Lamiapropria
Basallamina
•Low molarmassdrugscrosstheabove by passive
difussioncarriermediated systems ansselectiveand
non-selectiveendocytosis

17. ONTARGET
Transport across the epithelial barrier
•Thepolarmaterialsdiffusethroughtight
junctionsofepithelialcells
•Passivetransportisusuallyhigherindamagedmucosa
whereasactivetransportdependsonstructural
integrityofepithelialcells
•Positivelychargedparticlesshowedincreaseduptake
thannegativelychargedcounterparts.
•Absoptionofdrugsfrombuccalviatranscellularand
paracellularlaterbeingdominant.

18. ONTARGET
Transport across the epithelial barrier
•Someproposals
•Ex-vaginalcavity couldbean effective delivery
sitefor certainpharmaceuticals
•Such as calcitonin for the treatment of
postmenopausalosteoporosis
•It was demonstrated that when delivered vaginally
firstundergouterinepasseffect suggestingthatthe
vaginalroutecanbe useed totargettotheuterus

19. ONTARGET
Extravasation
•Manydiseasesresult fromthe dysfunctionof cells
locatedoutsidethecardiovascular systemthusfora
drugtoexertits therapeuticeffectsitmust exitfrom
the centralcirculationthisprocessoftrans vascular
exchangeiscalledExtravasation whichisgovernedby
blood capillarywalls
•Factors that control permeability of capillaries
•Structureofthecapillarywall
•Pathologicalcondition
•Rateofbloodandlymphsupply
•Physicochemicalfactorsofdrug

20. ONTARGET
Extravasation
•Thestructureofthe bloodcapillaryvariesin
differentorganstissues.
•Itconsistsofasinglelayerof endothelial cells
joinedtogetherbyintercellular juctions
•Dependingonthemorphologyandcontinuity ofthe
endotheliallayerandthe basement membraneblood
capillariesaredividedinto
•Continuous
•Fenestraded
•Sinusoidal

21. ONTARGET
Extravasation

22. ONTARGET
Extravasation
•Continuouscapillariesarecommonandwidely
distributedinthebodyexhibittightinterendothelial
junctionsandanuninterruptedbasementmembrane
•Fenestratedcapillariesshowsinter-
endothelialgapsof20-80nm
•Sinusoidalcapillariesshowinterendothelialgapsof
150nm
•Dependingonthetissueororganthebasalmembrane
iseitherabsentex-liverorpresentindiscontinuousex-
spleenandbonemarrow.

23. ONTARGET
Extravasation
•Macromoleculescantransversethenormal
endotheliumbypassiveprocesssuchasnonspecific
fluidphasetranscapillarypinocytosisandpassage
throughinterendothelialjunctionsgapsorfenestrate
orbyreceptor-mediatedtransportsystems
•Organssuchasthelungwithverylargesurfaceareas
haveaproportionatelylargetotalpermeabilityand
consequentlyahighextravasation
•Dependsonchargeshape,size,HLB,
characteristicsofmacromolecules.

24. ONTARGET
Extravasation
•Theendotheliumofbrainisthestrongestofall
endotheliaformedbycontinous nonfenestrated
endothelialcellswhichshownopinocyticactivity
•Solublemacromoleculespermeatetheendothelial
barriermorereadilythanparticulatemacromolecules
therateofmovementoffluidacrosstheendothelium
appearstobedirectlyrelatedtothediffbetweenthe
hydrostaticandosmoticforces.

25. ONTARGET
LymphaticUptake
•Followingextravasationdrug moleculescan either
reabsorbintothebloodstream directly or enter into
the lymphatic system andreturnwiththelymphto
theblood circulation
•Alsodrugsadministeredbysubcutaneous
intracellular transdermalperitonealroutes can
reachthesystemic circulationby lymphaticsystem.

26. ONTARGET
LymphaticUptake

27. ONTARGET
LymphaticUptake
•Factorsknowtoinfluencetheclearanceof
drugsfrominterstitialsites
Routeofadministration
Sizeandsurfacecharacteristicsofparticles
Formulationmedium
Thecompositionand
pHoftheinterstitialfluidand
Diseasewithintheinterstitium
•Thedirectdeliveryofdrugsintolymphaticshasbeen
proposedasapotentialapproachtokillmalignant
lymphoidcellslocatedinlymphnodes.

28. ONTARGET
References:
1.Muller,R;Keck,C(2004)."Challengesandsolutionsforthe
deliveryofbiotechdrugs–areviewofdrugnanocrystal
technologyandlipid
nanoparticles".JournalofBiotechnology113(1–3):
151–170.doi:10.1016/j.jbiotec.2004.06.007
2.Target-Oriented Drug Delivery Systems(9) by Vijay kumar
Modern Pharmaceutics Volume 2 ApplicationsandAdvances;
Fiftheditionedited by AlexanderT.FlorencePg.no329-342.
3.EncyclopaediaofcontrolleddeliverybyEdith
Mathiowitz.
4.S.PYyasandR.KKharControlleddrugDeliveryconceptsand
advancesVallabhprakashanfirstedition.