Vaccine mechanism, Types of vaccine delivery sytem

1. VACCINE DELIVERYVACCINE DELIVERY
SYSTEMSYSTEM
Prepared by: Ms Janu Vashi
Department of Pharmaceutics,
A R & G H P college of Pharmacy, V V
Nagar

2. CONTENTSCONTENTS

3. WHAT ARE VACCINES?WHAT ARE VACCINES?
AACQUIREDCQUIRED IIMMUNITYMMUNITY
WWEAKENEDEAKENED OROR KKILLEDILLED FORMSFORMS
TTOXINSOXINS
SSURFACEURFACE PROTEINSPROTEINS..

4. OVERVIEW OF HISTORY OF VACCINESOVERVIEW OF HISTORY OF VACCINES
VARIOLAE VACCINAE
--FFIIRSTRST VACCINEVACCINE WASWAS DEVELOPEDDEVELOPED ININ 19781978 FORFOR SSMALLMALL POX
BYBY EEDWARDDWARD JJENNERENNER..BYBY EEDWARDDWARD JJENNERENNER..
LLOUISOUIS PPASTEURASTEUR INVENTEDINVENTED RRABIESABIES VACCINEVACCINE 1985.1985.

6. HOW VACCINES WORKS?HOW VACCINES WORKS?
PROPHYLACTIC
TTHERAPEUTICHERAPEUTIC

8. SINGLE
COMPONENT
MULTI/ MIXED COMPONENTMULTI/ MIXED COMPONENT

9. -VACCINES CAN BE,
1)BACTERIAL VACCINE
2)VIRAL VACCINE
3)RICKETTSIAL VACCINE
4)TOXOIDS

10. TYPES OF VACCINES WHICH ARETYPES OF VACCINES WHICH ARE
COMMON IN USECOMMON IN USE
TYPE Live Vaccine Killed Vaccine
Bacterial Tuberculosis (BCG) Cholera
Typhoid
Whooping Cough
Viral Small Pox PolioViral Small Pox Polio
Rubella Influenza
Yellow Fever Rabies
Rickettsial Typhus
Toxoids Diphtheria
Tetanus

11. UPTAKE OF ANTIGENSUPTAKE OF ANTIGENS
--AANTIGENSNTIGENS GENERATEDGENERATED BYBY ENDOGENOUSENDOGENOUS ANDAND
EXOGENOUSEXOGENOUS ANTIGENANTIGEN PROCESSINGPROCESSING ACTIVATEACTIVATE
DIFFERENTDIFFERENT EFFECTOREFFECTOR FUNCTIONSFUNCTIONS

13. STAGES OF EXOGENOUS ANTIGENSTAGES OF EXOGENOUS ANTIGEN
UPTAKEUPTAKE
UUPTAKEPTAKE
AACCESSCCESS OFOF NATIVENATIVE ANTIGENSANTIGENS ANDAND PATHOGENSPATHOGENS TOTO
INTRACELLULARINTRACELLULAR PATHWAYSPATHWAYS OFOF DEGRADATIONDEGRADATION
DDEGRADATIONEGRADATION
LLLLIMITEDIMITED PROTEOLYSISPROTEOLYSIS OFOF ANTIGENSANTIGENS TOTO PEPTIDESPEPTIDES
AANTIGENNTIGEN--MHCMHC COMPLEXCOMPLEX FORMATIONFORMATION
LLOADINGOADING OFOF PEPTIDESPEPTIDES ONON MHCMHC MOLECULESMOLECULES
AANTIGENNTIGEN PPRESENTATIONRESENTATION
TTRANSPORTRANSPORT ANDAND EXPRESSIONEXPRESSION OFOF PEPTIDEPEPTIDE--MHCMHC COMPLEXESCOMPLEXES
ONON THETHE SURFACESSURFACES OFOF CELLSCELLS FORFOR REORGANIZATIONREORGANIZATION BYBY TT
CELLSCELLS

14. WHAT IS MHC?WHAT IS MHC?
MAJORMAJOR HISTOCOMPATIBILITYHISTOCOMPATIBILITY COMPLEXCOMPLEX (MHC)(MHC)
ACQUIREDACQUIRED IMMUNEIMMUNE SYSTEMSYSTEM
HISTOCOMPATIBILITYHISTOCOMPATIBILITYHISTOCOMPATIBILITYHISTOCOMPATIBILITY
--TTHEHE MAINMAIN FUNCTIONFUNCTION OFOF MHCMHC MOLECULESMOLECULES ISIS TOTO BINDBIND
TOTO ANTIGENSANTIGENS DERIVEDDERIVED FROMFROM PATHOGENSPATHOGENS ANDAND DISPLAYDISPLAY
THEMTHEM ONON THETHE CELLCELL SURFACESURFACE FORFOR RECOGNITIONRECOGNITION BYBY THETHE
APPROPRIATEAPPROPRIATE TT--CELLSCELLS

15. STAGES OF ENDOGENOUS ANTIGENSTAGES OF ENDOGENOUS ANTIGEN
UPTAKEUPTAKE UUPTAKEPTAKE
AANTIGENSNTIGENS//PATHOGENSPATHOGENS ALREADYALREADY PRESENTPRESENT ININ THETHE CELLSCELLS
DDEGRADATIONEGRADATION
AANTIGENSNTIGENS SYNTHESIZEDSYNTHESIZED ININ CYTOPLASMCYTOPLASM UNDERGOUNDERGO LIMITEDLIMITED
PROTEOLYTICPROTEOLYTIC DEGRADATIONDEGRADATION ININ THETHE CYTOPLASMCYTOPLASM
AANTIGENNTIGEN--MHC CMHC COMPLEXOMPLEX FORMATIONFORMATION
LLOADINGOADING OFOF PEPTIDEPEPTIDE ANTIGENSANTIGENS ONTOONTO MHC CMHC CLASSLASS II
MOLECULESMOLECULES ISIS DIFFERENTDIFFERENT TOTO THETHE LOADINGLOADING ONON MHCMHC CLASSCLASS-- IIII
MOLECULESMOLECULES
PPRESENTATIONRESENTATION
TTRANSPORTRANSPORT ANDAND EXPRESSIONEXPRESSION OFOF AANTIGENNTIGEN--MHC CMHC COMPLEXOMPLEX ONON
THETHE SURFACESURFACE OFOF CELLSCELLS FORFOR REORGANIZATIONREORGANIZATION BYBY TT CELLSCELLS

16. SINGLE SHOT VACCINESSINGLE SHOT VACCINES
AA SINGLESINGLE CONTACTCONTACT
POINTPOINT FORFOR PREVENTINGPREVENTING 44--66 DISEASESDISEASES..
--TTHEYHEY WILLWILL REPLACEREPLACE THETHE NEEDNEED FORFOR AA PRIMEPRIME BOOSTBOOST
REGIMENREGIMEN,, CONSEQUENTLYCONSEQUENTLY ELIMINATINGELIMINATING THETHE REPEATEDREPEATED
VISITSVISITS TOTO DOCTORSDOCTORS..
--TTHEHE COSTCOST FORFOR SINGLESINGLE SHOTSHOT VACCINESVACCINES AREARE HIGHERHIGHER ASAS--TTHEHE COSTCOST FORFOR SINGLESINGLE SHOTSHOT VACCINESVACCINES AREARE HIGHERHIGHER ASAS
COMPAREDCOMPARED TOTO NORMALNORMAL VACCINESVACCINES..
--DEFINATION:DEFINATION: TTHEHE
COMBINATIONCOMBINATION PRODUCTPRODUCT PRIMEPRIME COMPONENTCOMPONENT
ANTIGENANTIGEN MICROSPHEREMICROSPHERE COMPONENTCOMPONENT ANDAND
APPRAPPR ADJUVANTADJUVANT

18. --IINN ORDERORDER TOTO INCREASEINCREASE THETHE THERAPEUTICTHERAPEUTIC ACTIVITYACTIVITY
OFOF SINGLESINGLE SHOTSHOT VACCINESVACCINES VACCINEVACCINE ADJUVANTSADJUVANTS
AREARE USEDUSED..

19. PPARTICULATEARTICULATE AADJUVENTSDJUVENTS
--TTHEYHEY FORMFORM VERYVERY SMALLSMALL PARTICLESPARTICLES THATTHAT CANCAN STIMULATESTIMULATE
THETHE IMMUNEIMMUNE SYSTEMSYSTEM ANDAND ALSOALSO ENHANCESENHANCES THETHE DELIVERYDELIVERY
OFOF ANTIGENANTIGEN TOTO IMMUNEIMMUNE CELLSCELLS..
--EEXAMPLESXAMPLES OFOF PARTICULATEPARTICULATE ADJUVENTSADJUVENTS AREARE::
1)A1)ALUMLUM
--MMOSTOST COMMONLYCOMMONLY USEDUSED ADJUVANTADJUVANT
--CONSISTSCONSISTS OFOF AALUMINUMLUMINUM SSALTSALTS THATTHAT AREARE NOTNOT SOLUBLESOLUBLE ININ
WATERWATER
--RRECENTLYECENTLY ITIT ISIS USEDUSED ININ VACCINESVACCINES FORFOR HHEPATITISEPATITIS BB
--MECHANISMMECHANISM ISIS UNKNOWNUNKNOWN FORFOR HOWHOW ITIT STIMULATESSTIMULATES
VACCINEVACCINE INDUCEDINDUCED IMMUNITYIMMUNITY..

20. 2)V2)VIROSOMESIROSOMES
FLUFLU VACCINEVACCINE HHEPATITISEPATITIS AA
VACCINEVACCINE
ANTIGENSANTIGENS ANDAND OTHEROTHER PROTEINSPROTEINS ONON THEIRTHEIR SURFACESURFACE,,
DOESDOES
NOTNOT CONTAINCONTAIN ANYANY GENETICGENETIC MATERIALMATERIAL..
MMECHANISMECHANISM::

21. 3)C3)CYTOKINESYTOKINES
-- TTHEYHEY AREARE SMALLSMALL PROTEINSPROTEINS THATTHAT SERVESSERVES ASAS CHEMICALCHEMICAL
MESSENGERMESSENGER OFOF THETHE IMMUNEIMMUNE SYSTEMSYSTEM..
--BBECAUSEECAUSE OFOF THEIRTHEIR ROLEROLE ININ IMMUNEIMMUNE RESPONSESRESPONSES,, SOMESOME
CYTOKINESCYTOKINES HAVEHAVE BEENBEEN EVALUATEDEVALUATED ASAS VACCINEVACCINE
ADJUVENTSADJUVENTS..ADJUVENTSADJUVENTS..
-- SOMETIMESSOMETIMES THESETHESE ADJUVENTSADJUVENTS AREARE USEDUSED ININ
COMBINATIONSCOMBINATIONS FORFOR PRODUCINGPRODUCING PROPORTIONALPROPORTIONAL
IMMUNEIMMUNE RESPONSESRESPONSES..

22. MUCOSAL VACCINEMUCOSAL VACCINE
DELIVERY SYSTEMDELIVERY SYSTEM

23. MAJORMAJOR PORTALPORTAL OFOF ENTRYENTRY
FORFOR MANYMANY HUMANHUMAN PATHOGENSPATHOGENS
MOREMORE
EFFECTIVEEFFECTIVE
ATAT THEIRTHEIR SITESSITES OFOF ENTRYENTRY..
UPTAKEUPTAKE BYBY LOCALLOCAL ANTIGENANTIGEN--PRESENTINGPRESENTING CELLSCELLS

24. SURFACESURFACE AREAAREA (400(400 MM2)2)
200200 TIMESTIMES GREATERGREATER THANTHAN THATTHAT OFOF THETHE SKINSKIN..
TYPETYPE--II ANDAND TYPETYPE--IIII MUCOSAMUCOSA.. TTYPEYPE--II MUCOSAMUCOSA
LUNGLUNG ANDAND GUTGUT TYPETYPE--IIII
MUCOSAMUCOSA SURFACESSURFACES OFOF THETHE MOUTHMOUTH,,
ESOPHAGUSESOPHAGUS ANDAND CORNEACORNEA..

25. DESIGN AND STRATEGIES FORDESIGN AND STRATEGIES FOR
MUCOSAL DELIVERYMUCOSAL DELIVERYMUCOSAL DELIVERYMUCOSAL DELIVERY

26. --EEMULSIONSMULSIONS AREARE HETEROGENEOUSHETEROGENEOUS LIQUIDLIQUID SYSTEMSSYSTEMS MAYMAY BEBE
WATERWATER--ININ--OILOIL EMULSIONSEMULSIONS((WW//OO),),OILOIL ININ WATERWATER
EMULSIONSEMULSIONS((OO//WW),),OROR MOREMORE COMPLEXCOMPLEX SYSTEMSSYSTEMS SUCHSUCH ASAS
WATERWATER--ININ--OILOIL--ININ--WATERWATER((WW//OO//WW))MULTIPLEMULTIPLE EMULSIONSEMULSIONS,,
MICROMICRO EMULSIONSEMULSIONS,, OROR NANONANO EMULSIONSEMULSIONS
--AANTIGENSNTIGENS AREARE DISSOLVEDDISSOLVED ININ AA WATERWATER PHASEPHASE ANDAND
I)Emulsion type delivery
--AANTIGENSNTIGENS AREARE DISSOLVEDDISSOLVED ININ AA WATERWATER PHASEPHASE ANDAND
EMULSIFIEDEMULSIFIED ININ THETHE OILOIL ININ THETHE PRESENCEPRESENCE OFOF ANAN
APPROPRIATEAPPROPRIATE EMULSIFIEREMULSIFIER..
--TTHEHE CONTROLLEDCONTROLLED RELEASERELEASE CHARACTERISTICSCHARACTERISTICS OFOF ANAN
EMULSIONEMULSION AREARE DETERMINEDDETERMINED BYBY FACTORSFACTORS SUCHSUCH ASAS
VISCOSITYVISCOSITY OFOF OILOIL PHASEPHASE,, OILOIL--TOTO--WATERWATER PHASEPHASE RATIORATIO ANDAND
EMULSIONEMULSION DROPLETDROPLET SIZESIZE..

27. --EE..GG.. HIGHHIGH OILOIL CONTENTCONTENT CANCAN CAUSECAUSE UNNECESSARYUNNECESSARY
INJECTIONINJECTION SITESITE IRRITATIONIRRITATION ANDAND TOOTOO LARGELARGE AA DROPLETDROPLET SIZESIZE
CANCAN RESULTRESULT ININ AA PHYSICALLYPHYSICALLY UNSTABLEUNSTABLE PRODUCTPRODUCT THERETHERE BYBY
REDUCINGREDUCING ITSITS SHELFSHELF LIFELIFE..
--HHUANGUANG ETET DEVELOPEDDEVELOPED AA NOVELNOVEL EMULSIONEMULSION--TYPETYPE
VACCINEVACCINE DELIVERYDELIVERY SYSTEMSSYSTEMS OFOF THETHE AMPHIPHILICAMPHIPHILICVACCINEVACCINE DELIVERYDELIVERY SYSTEMSSYSTEMS OFOF THETHE AMPHIPHILICAMPHIPHILIC
BIORESORBABLEBIORESORBABLE POLYMERPOLYMER POLYPOLY((ETHYLENEETHYLENE GLYCOLGLYCOL))--
BLOCKBLOCK--POLYPOLY((LACTIDELACTIDE--COCO--EPSILONEPSILON--CAPROLACTONECAPROLACTONE))
(PEG(PEG--BB--PLACL)PLACL) USINGUSING OOVALBUMINVALBUMIN ASAS MODELMODEL
ANTIGENANTIGEN..

28. --RRESULTSESULTS FROMFROM PHYSICOCHEMICALPHYSICOCHEMICAL CHARACTERIZATIONCHARACTERIZATION
STUDIESSTUDIES ANDAND ININ-- VITROVITRO RELEASERELEASE STUDIESSTUDIES SHOWEDSHOWED THATTHAT
THEYTHEY AREARE COMPOSEDCOMPOSED OFOF HOMOGENOUSHOMOGENOUS FINEFINE PARTICLESPARTICLES
--AADVANTAGESDVANTAGES::
--DDISADVANTAGESISADVANTAGES::

29. --LLIPOSOMESIPOSOMES AREARE SPHERICALSPHERICAL SHAPESHAPE VESICLESVESICLES
CONTAININGCONTAINING ANAN AQUEOUSAQUEOUS CORECORE WHICHWHICH ISIS ENCLOSEDENCLOSED
BYBY AA LIPIDLIPID BIBI--LAYERLAYER..
II)Liposome Based delivery
PHOSPHATIDYLCHOLINEPHOSPHATIDYLCHOLINE,,
EGGPHOSPHATIDYLEGGPHOSPHATIDYL--
ETHANOLAMINEETHANOLAMINE..

30. PPREPARATIONREPARATION OFOF LLIPOSOMEIPOSOME VACCINEVACCINE DELIVERYDELIVERY
SYSTEMSYSTEM
WATERWATER--
SOLUBLESOLUBLE ANTIGENSANTIGENS
ENTRAPPEDENTRAPPED WITHINWITHIN THETHE
AQUEOUSAQUEOUS INNERINNER SPACESPACE OFOF LIPOSOMESLIPOSOMES
LLIPOPHILICIPOPHILIC COMPOUNDSCOMPOUNDS
INTERCALATEDINTERCALATED INTOINTO
THETHE LIPIDLIPID BILAYERBILAYER
ADSORPTIONADSORPTION STABLESTABLE
CHEMICALCHEMICAL LINKINGLINKING..

32. AADVANTAGESDVANTAGES::
DDISADVANTAGESISADVANTAGES::

33. SUBMICRONSUBMICRON--
SIZEDSIZED COLLOIDALCOLLOIDAL PARTICLESPARTICLES
III)Polymeric Nano Particles

34. --BBIODEGRADABLEIODEGRADABLE PPOLYOLY(A(ALKYLLKYL CYANOCYANO--ACRYLATEACRYLATE) (PACA)) (PACA)
OVALBUMINOVALBUMIN
--BBIODEGRADABLEIODEGRADABLE PPOLYOLY(M(METHYLETHYL METHAMETHA ACRYLATEACRYLATE))
(PMMA)(PMMA)

35. VIROSOMEVIROSOME
UNILAMELLARUNILAMELLAR PHOSPHOLIPIDPHOSPHOLIPID MEMBRANEMEMBRANE~150~150
MMMM
VIRUSVIRUS DERIVEDDERIVED PROTEINSPROTEINS TT
ENABLEENABLE THETHE VIROSOMEVIROSOME MEMBRANESMEMBRANES TOTO FUSEFUSE
IV)Virosomes
ENABLEENABLE THETHE VIROSOMEVIROSOME MEMBRANESMEMBRANES TOTO FUSEFUSE
WITHWITH CELLSCELLS OFOF DELIVERDELIVER THETHE
SPECIFICSPECIFIC ANTIGENSANTIGENS DIRECTLYDIRECTLY TOTO THEIRTHEIR TARGETTARGET CELLSCELLS
COMPLETELYCOMPLETELY DEGRADEDDEGRADED WITHINWITHIN THETHE CELLSCELLS..

36. CONTRIBUTESCONTRIBUTES TOTO THETHE IMMUNOLOGICALIMMUNOLOGICAL
PROPERTIESPROPERTIES

38. V)Melt In Mouth strips
--FFIRSTIRST DESIGNEDDESIGNED BYBY
UNDERGRADUATEUNDERGRADUATE STUDENTSSTUDENTS
ATAT JJOHNSOHNS HHOPKINSOPKINS
UUNIVERSITYNIVERSITY ONON BIOMEDICALBIOMEDICAL
ENGINEERINGENGINEERING DESIGNDESIGN DAYDAY
FORFOR PROTECTIONPROTECTION AGAINSTAGAINST
ROTAROTA VIRUSVIRUS INFECTIONINFECTION

39. MOUTH DISSOLVING STRIPSMOUTH DISSOLVING STRIPS

40. LIQUIDLIQUID OROR FREEZEFREEZE--DRIEDDRIED
FORMFORM

41. TTRANSDERMALRANSDERMAL VACCINEVACCINE
DELIVERYDELIVERY SYSTEMSYSTEM

42. INTRODUCTIONINTRODUCTION
LARGESTLARGEST MOSTMOST ACCESSIBLEACCESSIBLE ORGANORGAN
EASEEASE OFOF ACCESSACCESS,, AA POTENTIALPOTENTIAL
FORFOR BOTHBOTH SYSTEMICSYSTEMIC ANDAND MUCOSALMUCOSALFORFOR BOTHBOTH SYSTEMICSYSTEMIC ANDAND MUCOSALMUCOSAL
IMMUNEIMMUNE RESPONSERESPONSE..

43. SKIN AS A SITE OF VACCINE DELIVERYSKIN AS A SITE OF VACCINE DELIVERY
1)P1)PHYSICALHYSICAL BBARRIERSARRIERS
STRATUMSTRATUM CORNEUMCORNEUM
LARGELARGE MOLECULESMOLECULES SUCHSUCH ASAS VACCINESVACCINES..

44. 2)E2)ENZYMATICNZYMATIC BBARRIERARRIER
3)I3)IMMUNOLOGICALMMUNOLOGICAL BBARRIERSARRIERS

46. DESIGN AND STRATERGY FORDESIGN AND STRATERGY FOR
TRANSDERMAL VACCINE DELIVERYTRANSDERMAL VACCINE DELIVERYTRANSDERMAL VACCINE DELIVERYTRANSDERMAL VACCINE DELIVERY

47. AA HIGHHIGH--VELOCITYVELOCITY JETJET
100100 TOTO 200200 MM//SS
I)Liquid Jet Injectors
I)I) MULTIMULTI--USEUSE NOZZLENOZZLE JETJET INJECTORSINJECTORS (MUNJI(MUNJISS))
II)II) DISPOSABLEDISPOSABLE CARTRIDGECARTRIDGE JETJET
INJECTORSINJECTORS (DCJI(DCJISS))

48. AA))POWERPOWER SOURCESOURCE ((COMPRESSEDCOMPRESSED GASGAS OROR SPRINGSPRING))
BB))PISTONPISTON
CC))DRUGDRUG OROR VACCINEVACCINE--LOADEDLOADED COMPARTMENTCOMPARTMENT
DD))APPLICATIONAPPLICATION NOZZLENOZZLE,, WITHWITH TYPICALTYPICAL ORIFICEORIFICE SIZESIZE ININ THETHE
RANGERANGE OFOF 150150 TOTO 300300 µMµM

49. WORKING OF JET INJECTORSWORKING OF JET INJECTORS
MICROSECONDSMICROSECONDS..

51. APPLICATIONS OF JET INJECTORSAPPLICATIONS OF JET INJECTORS
1)A1)APPLICATIONSPPLICATIONS OFOF LIQUIDLIQUID--JETJET INJECTORSINJECTORS HAVEHAVE BEENBEEN
FOCUSEDFOCUSED ONON DELIVERYDELIVERY OFOF MACROMOLECULESMACROMOLECULES THATTHAT DODO NOTNOT
PASSIVELYPASSIVELY PERMEATEPERMEATE THETHE SKINSKIN..
2)2)ITIT HASHAS BEENBEEN SHOWNSHOWN TOTO INCREASEINCREASE IMMUNEIMMUNE RESPONSESRESPONSES TOTO
DNADNA-- ..BOTHBOTH CONVENTIONALCONVENTIONAL ANDAND DNADNA--BASEDBASED VACCINESVACCINES..
E.E.GG.. HEPATITISHEPATITIS AA VACCINEVACCINE OROR AA INFLUENZAINFLUENZA VACCINEVACCINE,, WEREWERE
FOUNDFOUND TOTO BEBE INCREASEDINCREASED BYBY ATAT LEASTLEAST 10%10% WHENWHEN USINGUSING
NEEDLENEEDLE--FREEFREE INJECTIONSINJECTIONS COMPAREDCOMPARED TOTO NEEDLENEEDLE ANDAND
SYRINGESYRINGE ADMINISTRATIONADMINISTRATION

52. DEMERITS OF JET INJECTION TECHNOLOGYDEMERITS OF JET INJECTION TECHNOLOGY
1)P1)PAINAIN ANDAND BRUISINGBRUISING ATAT THETHE SITESITE OFOF ADMINISTRATIONADMINISTRATION..
ELECTRICELECTRIC TRANSDUCERTRANSDUCER

53. VVISIONISION®® CCHOICEHOICE®®
VV--GGOO MMINIINI--JJECTECT
BBIOJECTORIOJECTOR 20002000 PPENENJJETETBBIOJECTORIOJECTOR 20002000 PPENENJJETET
IINJEXNJEX
ZZENEOENEO

54. II)Epidermal Powder Immunization
TTHEHE DEVICEDEVICE DESIGNDESIGN PRINCIPLESPRINCIPLES AREARE SIMILARSIMILAR TOTO LIQUIDLIQUID
INJECTORSINJECTORS,, WITHWITH AA POWDERPOWDER COMPARTMENTCOMPARTMENT ANDAND
COMPRESSEDCOMPRESSED CARRIERCARRIER GASGAS,, SUCHSUCH ASAS HELIUMHELIUM. U. UPONPON
ACTUATIONACTUATION,, THETHE PARTICLESPARTICLES AREARE CARRIEDCARRIED BYBY THETHE GASGAS,, TOTO
IMPACTIMPACT THETHE SKINSKIN SURFACESURFACE ATAT HIGHHIGH VELOCITYVELOCITY,, PUNCTURINGPUNCTURING
MICRONMICRON--SIZEDSIZED HOLESHOLES ININ THETHE EPIDERMISEPIDERMIS TOTO FACILITATEFACILITATE SKINSKIN
DEPOSITIONDEPOSITION

55. --UUPONPON ACTUATIONACTUATION,, THETHE PARTICLESPARTICLES AREARE CARRIEDCARRIED BYBY THETHE GASGAS,,
TOTO IMPACTIMPACT THETHE SKINSKIN SURFACESURFACE ATAT HIGHHIGH VELOCITYVELOCITY,,
PUNCTURINGPUNCTURING MICRONMICRON--SIZEDSIZED HOLESHOLES ININ THETHE EPIDERMISEPIDERMIS TOTO
FACILITATEFACILITATE SKINSKIN DEPOSITIONDEPOSITION..
ADVANTAGESADVANTAGES
FORMULATIONFORMULATION ANDAND STABILITYSTABILITY ISSUESISSUES..FORMULATIONFORMULATION ANDAND STABILITYSTABILITY ISSUESISSUES..
PARTICLEPARTICLE BOMBARDMENTBOMBARDMENT OFFERSOFFERS ADVANTAGESADVANTAGES WITHWITH REGARDREGARD
TOTO LLANGERHANSANGERHANS CELLCELL TARGETINGTARGETING ANDAND IMMUNEIMMUNE SYSTEMSYSTEM
ACTIVATIONACTIVATION

56. III)Colloidal Carriers

57. A)NANO PARTICLES AND NANO CARRIERSA)NANO PARTICLES AND NANO CARRIERS
--NNANOPARTICLESANOPARTICLES ANDAND MICROPARTICLESMICROPARTICLES AREARE POLYMERICPOLYMERIC
PARTICLESPARTICLES ININ THETHE NANOMETERNANOMETER ANDAND MICROMETREMICROMETRE SIZESIZE RANGERANGE
RESPECTIVELYRESPECTIVELY..
--CCOMPOUNDSOMPOUNDS CANCAN BEBE INCORPORATEDINCORPORATED INTOINTO THETHE PARTICLESPARTICLES
ININ FORMFORM OFOF AA SOLIDSOLID DISPERSIONDISPERSION OROR AA SOLIDSOLID SOLUTIONSOLUTION,, ORORININ FORMFORM OFOF AA SOLIDSOLID DISPERSIONDISPERSION OROR AA SOLIDSOLID SOLUTIONSOLUTION,, OROR
BOUNDBOUND TOTO THETHE PARTICLEPARTICLE SURFACESURFACE BYBY PHYSICALPHYSICAL ADSORPTIONADSORPTION
ANDAND CHEMICALCHEMICAL BINDINGBINDING
--THUSTHUS ALLOWINGALLOWING THETHE PARTICLESPARTICLES TOTO ACTACT ASAS CARRIERSCARRIERS OROR ASAS
ADJUVANTSADJUVANTS FORFOR THETHE VACCINEVACCINE..

58. PPROBLEMSROBLEMS ASSOCIATEDASSOCIATED
--BBUTUT THETHE GENERALGENERAL PROBLEMPROBLEM ISIS THATTHAT
NANOPARTICLESNANOPARTICLES ADMINISTEREDADMINISTERED TOTO THETHE SKINSKIN DODO NOTNOTNANOPARTICLESNANOPARTICLES ADMINISTEREDADMINISTERED TOTO THETHE SKINSKIN DODO NOTNOT
PERMEATEPERMEATE THETHE INTACTINTACT STRATUMSTRATUM CORNEUMCORNEUM,, BUTBUT MAYMAY
ACCUMULATEACCUMULATE ININ HAIRHAIR FOLLICLESFOLLICLES. S. SOO THEIRTHEIR
POTENTIALPOTENTIAL UTILITYUTILITY FORFOR PASSIVEPASSIVE TRANSDERMALTRANSDERMAL
VACCINEVACCINE DELIVERYDELIVERY ISIS LIMITEDLIMITED..

59. B)LB)LIPOSOMESIPOSOMES ANDAND ELASTICELASTIC VESICLESVESICLES

60. ““SQUEEZESQUEEZE THROUGHTHROUGH””
LIMITATIONSLIMITATIONS

61. IV)Energy Based Approaches

62. A)EA)ELECTROPORATIONLECTROPORATION
--EELECTROPORATIONLECTROPORATION INVOLVESINVOLVES THETHE ADMINISTRATIONADMINISTRATION OFOF
ELECTRICALELECTRICAL PULSESPULSES TOTO CREATECREATE TRANSIENTTRANSIENT PORESPORES ININ THETHE SKINSKIN
ANDAND THUSTHUS INCREASEINCREASE THETHE SKINSKIN PERMEABILITYPERMEABILITY TOTO DRUGSDRUGS ANDAND
MACROMOLECULESMACROMOLECULES..
-- IINOVIONOVIO BBIOMEDICALIOMEDICAL CCORPORATIONORPORATION HASHAS DEVELOPEDDEVELOPED AA-- IINOVIONOVIO BBIOMEDICALIOMEDICAL CCORPORATIONORPORATION HASHAS DEVELOPEDDEVELOPED AA
SERIESSERIES OFOF HANDHAND--HELDHELD,, CORDLESSCORDLESS ELECTROPORATIONELECTROPORATION
DEVICESDEVICES THATTHAT HAVEHAVE BEENBEEN USEDUSED ININ VACCINEVACCINE DELIVERYDELIVERY
STUDIESSTUDIES..
-- DDELIVERYELIVERY OFOF DNADNA VACCINESVACCINES INTOINTO MUSCLEMUSCLE OROR SKINSKIN TISSUETISSUE
WITHWITH ELECTROPORATIONELECTROPORATION SYSTEMSSYSTEMS GENERATEDGENERATED ROBUSTROBUST
IMMUNEIMMUNE RESPONSESRESPONSES

64. B)UB)ULTRASOUNDLTRASOUND OROR SONOPHORESISSONOPHORESIS
-- LLOWOW FREQUENCYFREQUENCY SONOPHORESISSONOPHORESIS INVOLVESINVOLVES APPLICATIONAPPLICATION
OFOF ULTRASOUNDULTRASOUND WAVESWAVES ATAT FREQUENCIESFREQUENCIES BETWEENBETWEEN 2020 TOTO
100100 KKHHZZ TOTO THETHE SKINSKIN SURFACESURFACE TOTO REDUCEREDUCE THETHE STRATUMSTRATUM
CORNEUMCORNEUM BARRIERBARRIER ANDAND THEREBYTHEREBY INCREASEINCREASE SKINSKIN
PERMEABILITYPERMEABILITY..
--PRETREATMENTPRETREATMENT ISIS GIVENGIVEN PRIORPRIOR TOTO THETHE APPLICATIONAPPLICATION OFOF AA--PRETREATMENTPRETREATMENT ISIS GIVENGIVEN PRIORPRIOR TOTO THETHE APPLICATIONAPPLICATION OFOF AA
DRUGDRUG SOLUTIONSOLUTION OROR PATCHPATCH..
--LLOWOW FREQUENCYFREQUENCY ULTRASOUNDULTRASOUND (20(20 KKHHZZ)) WASWAS USEDUSED TOTO
DELIVERDELIVER AA TETANUSTETANUS TOXOIDTOXOID,, ELICITINGELICITING AA ROBUSTROBUST IMMUNEIMMUNE
RESPONSERESPONSE ININ MICEMICE TOTO MICEMICE..
--AA COMMERCIALCOMMERCIAL ULTRASOUNDULTRASOUND DEVICEDEVICE,, SSONOONOPPREPREP,, FORFOR
ADMINISTRATIONADMINISTRATION OFOF LOCALLOCAL ANESTHETICANESTHETIC,, WASWAS LAUNCHEDLAUNCHED ININ
20042004 BUTBUT WITHDRAWNWITHDRAWN ININ 2007.2007.

66. C)TC)THERMALHERMAL ABLATIONABLATION OROR MICROPORATIONMICROPORATION
1)P1)PASSASSPPORTORT®® SYSTEMSYSTEM BYBY AALTEALTEA TTHERAPEUTICSHERAPEUTICS CCORPORP
(A(ALTANTALTANTA, GA), GA)
2)V2)VIAIADDERMERM®® DEVICEDEVICE BYBY TTRANSRANSPPHARMAHARMA LLTDTD (I(ISRAELSRAEL).).

68. D)MD)MICRONEEDLESICRONEEDLES
POINTEDPOINTED MICROMICRO--SIZEDSIZED
PROJECTIONSPROJECTIONS,, FABRICATEDFABRICATED INTOINTO ARRAYSARRAYS
AA))SOLIDSOLID MICRONEEDLESMICRONEEDLES FORFOR PERMEABILIZINGPERMEABILIZING SKINSKIN VIAVIA
FORMATIONFORMATION OFOF MICRONMICRON--SIZEDSIZED HOLESHOLES
--

70. BB))SOLIDSOLID MICRONEEDLESMICRONEEDLES COATEDCOATED WITHWITH DRYDRY DRUGDRUG OROR
VACCINEVACCINE
CC))POLYMERICPOLYMERIC MICRONEEDLESMICRONEEDLES WITHWITH ENCAPSULATEDENCAPSULATED DRUGDRUGCC))POLYMERICPOLYMERIC MICRONEEDLESMICRONEEDLES WITHWITH ENCAPSULATEDENCAPSULATED DRUGDRUG
OROR VACCINEVACCINE

72. DD)) HOLLOWHOLLOW MICRONEEDLESMICRONEEDLES
--

73. References
1)T1)TEXTBOOKEXTBOOK OFOF PPHARMACEUTICALHARMACEUTICAL MMICROBIOLOGYICROBIOLOGY BYBY N KN K
JJAINAIN
2) M2) MUCOSALUCOSAL VVACCINEACCINE DDESIGNESIGN ANDAND DDELIVERYELIVERY BYBY KKIMIM A.A.
WWOODROWOODROW,1 K,1 KAILAAILA M. BM. BENNETTENNETT,2,3,2,3 ANDAND DDAVIDAVID D. LD. LOO22WWOODROWOODROW,1 K,1 KAILAAILA M. BM. BENNETTENNETT,2,3,2,3 ANDAND DDAVIDAVID D. LD. LOO22
3) T3) TRANSDERMALRANSDERMAL DELIVERYDELIVERY OFOF VACCINESVACCINES BYBY SSARIKAARIKA
NNAMJOSHIAMJOSHI ANDAND HHEATHEREATHER A.E. BA.E. BENSONENSON CCURTINURTIN HHEALTHEALTH
IINNOVATIONNNOVATION RRESEARCHESEARCH IINSTITUTENSTITUTE