Critical Reviews in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v13.i3-4.30 pages 257- !!

Trans"ers#mes$ %ip#s#mes an& Other %ipi& Suspensi#ns #n the S'in: (ermeati#n )nhancement$ *esicle (enetrati#n$ an& Trans&ermal Drug Delivery
+reg#r Cevc Medizinische Biophysik, Technische Universitt Mnchen, Klinikum r.d.l., Ismaningerstr. , !"#$%&' Mnchen ,-STR,CT Agents with M( are being e!ivere trans er"a!!y with the ai #$ s%in &er"eati#n enhan'ers that in'rease the agent(s i$$usivity an /#r &artiti#ning in the #rgan. )se #$ '#"&#site* !i&i i' agent-'arriers +!i&#s#"es* ni#s#"es, was n#t su''ess$u! t# ate* ue t# the inabi!ity #$ su'h vehi'!es t# &ass thr#ugh the narr#w + 30 n", inter'e!!u!ar &assages +virtua! &#res, in the #uter s%in !ayers. A s#!uti#n t# this &r#b!e" are the #r ers #$ "agnitu e "#re e$#r"ab!e su&ra"#!e'u!ar aggregates* trans$ers#"es. Su'h inn#vative rug-'arriers are riven a'r#ss the s%in by the n#tura!!y #''urring* '#n'entrati#n-insensitive* an &r#bab!y hy rati#n base * transe&i er"a! gra ient+s, an trans&#rt very e$$i'ient +-- 50., an re&r# u'ib!y vari#us agents +/00 M( 1060 !i&#&hi!i'/ hy r#&hi!i', int# the b# y. Trans$ers#"es were su''ess$u!!y use in ani"a!s an hu"ans* a!s# $#r the trans'utane#us &e&ti e an &r#tein e!ivery. The the#reti'a! rati#na! $#r this is es'ribe t#gether with the '#rres&#n ing e1&eri"enta! "# e!s an &ra'ti'a! e1a"&!es. .eyw#r&s: trans&ermal &elivery$ lipi& vesicles$ trans"ers#mes$ the#retical m#&els$ in viv# stu&ies$ s'in penetrati#n$ permeati#n enhancement

/#vel mechanisms an& &evices t# ena0le success"ul trans&ermal &rug &elivery

2.3 2arry

Drug De!ivery 4r#u&* S'h##! #$ 5har"a'y* )niversity #$ 2ra $#r * 2ra $#r 2D6 1D5* )7

Review

Trans"ers#mes "#r trans&ermal &rug &elivery

8#ve"ber /006* 9#!. 3* 8#. 6 * 5ages 6/6-636 + #i:10.1516/164/5/46.3.6.6/6, ;T<= 5D> +51? 72, 5D> 5!us +563 72, Re&rints 5er"issi#ns

;eather A@ 2ens#n Curtin )niversity #$ Te'hn#!#gy* S'h##! #$ 5har"a'y* 45A 2#1 )1?B6* 5erth* 3A 6B45* Austra!ia. h.bens#nC'urtin.e u.au

Trans$ers#"esD +E ea A4, are a $#r" #$ e!asti' #r e$#r"ab!e vesi'!e* whi'h were $irst intr# u'e in the ear!y 1??0s. @!asti'ity is generate by in'#r&#rati#n #$ an e ge a'tivat#r in the !i&i bi!ayer stru'ture. The #rigina! '#"&#siti#n #$ these vesi'!es was s#ya &h#s&hati y! 'h#!ine in'#r&#rating s# iu" 'h#!ate an a s"a!! '#n'entrati#n #$ ethan#!. Trans$ers#"es are a&&!ie in a n#n-#''!u e "eth# t# the s%in an have been sh#wn t# &er"eate thr#ugh the stratu" '#rneu" !i&i !a"e!!ar regi#ns as a resu!t #$ the hy rati#n #r #s"#ti' $#r'e in the s%in. They have been use as rug 'arriers $#r a range #$ s"a!! "#!e'u!es* &e&ti es* &r#teins an va''ines* b#th in vitro an in vivo. Et has been '!ai"e by E ea A4 that inta't Trans$ers#"es &enetrate thr#ugh the stratu" '#rneu" an the un er!ying viab!e s%in int# the b!## 'ir'u!ati#n. ;#wever* this has n#t been substantiate by #ther resear'h gr#u&s wh# have e1tensive!y &r#be the "e'hanis" #$ &enetrati#n an intera'ti#n #$ e!asti' vesi'!es in the s%in. Stru'tura! 'hanges in the stratu" '#rneu" have been i enti$ie * an inta't e!asti' vesi'!es visua!ise within the stratu" '#rneu" !i&i !a"e!!ar regi#ns* but n# inta't vesi'!es have been as'ertaine in the viab!e tissues. )sing the &rin'i&!e #$ in'#r&#rating an e ge-a'tivat#r agent int# a bi!ayer stru'ture* a nu"ber #$ #ther e!asti' vesi'!e '#"&#siti#ns have been eva!uate . This review es'ribes the resear'h int# the eve!#&"ent an eva!uati#n #$ Trans$ers#"es an e!asti' vesi'!es as t#&i'a! an trans er"a! e!ivery syste"s.

.eyw#r&s
'#!!#i s* e!asti' vesi'!es* !i&#s#"es* s%in &enetrati#n enhan'e"ent* u!tra e$#r"ab!e vesi'!es

Rea <#re: htt&://in$#r"ahea!th'are.'#"/ #i/abs/10.1516/164/5/46.3.6.6/6

Trans"ers#mes1, /#vel *esicular Carrier "#r )nhance& Trans&ermal Delivery: Devel#pment$ Characteri2ati#n$ an& (er"#rmance )valuati#n
/003* 9#!. /?* 8#. ? * 5ages 1013-10/6 ;T<= 5D> +366 72, 5D> 5!us +3B/ 72, Re&rints 5er"issi#ns

Subheet Fain* <.5har".* 5ariGat Fain* <.S.* R. 2. )"a"aheshwari* <.5har". an 8. 7. Fain* 5h.D. 5har"a'euti's Resear'h =ab#rat#ry* De&art"ent #$ 5har"a'euti'a! S'ien'es* Dr. ;ari Singh 4#ur )niversity* Sagar +<.5.,* En ia 5har"a'euti's Resear'h =ab#rat#ry* De&art"ent #$ 5har"a'euti'a! S'ien'es* Dr. ;ari Singh 4#ur )niversity* Sagar +<.5.,* 460 003* En ia* 00?1-65B/-///163 Gnaren rCyah##.'#.in

,0stract
This w#r% es'ribes the use #$ a n#ve! vesi'u!ar rug 'arrier syste" 'a!!e trans$ers#"es* whi'h is '#"&#se #$ &h#s&h#!i&i * sur$a'tant* an water $#r enhan'e trans er"a! e!ivery. The trans$ers#"a! syste" was "u'h "#re e$$i'ient at e!ivering a !#w an high "#!e'u!ar weight rug t# the s%in in ter"s #$ Huantity an e&th. En the &resent stu y trans$ers#"es an !i&#s#"es were &re&are by using e1a"ethas#ne as a "# e! rug. The syste" was eva!uate in vitr# $#r vesi'!e sha&e an siIe* entra&"ent e$$i'ien'y* egree #$ e$#r"abi!ity* nu"ber #$ vesi'!es &er 'ubi' ""* an rug i$$usi#n a'r#ss the arti$i'ia! "e"brane an rat s%in. The e$$e'ts #$ sur$a'tant ty&e* '#"&#siti#n* 'harge* an '#n'entrati#n #$ sur$a'tant were stu ie . The in viv# &er$#r"an'e #$ se!e'te $#r"u!ati#n was eva!uate by using a 'arrageenan-in u'e rat &aw e e"a "# e!. >!u#res'en'e "i'r#s'#&y by using rh# a"ine1/3 an 6-'arb#1y$!u#res'ein as $!u#res'en'e &r#be was &er$#r"e . The stabi!ity stu y was &er$#r"e at 4JC an 36JC. An in vitr# rug re!ease stu y has sh#wn a near!y Ier# #r er re!ease #$ rug an n# !ag &hase. The absen'e #$ !ag &hase in '#"&aris#n t# !i&#s#"es an #int"ent is attribute t# the greater e$#r"abi!ity* whi'h "ay a''#unt $#r better s%in &er"eabi!ity #$ trans$ers#"es. En viv# stu ies #$ trans$ers#"es sh#we better antie e"a a'tivity in '#"&aris#n t# !i&#s#"es an #int"ent* in i'ating better &er"eati#n thr#ugh the &enetrati#n barrier #$ the s%in. This was $urther '#n$ir"e thr#ugh a $!u#res'en'e "i'r#s'#&y stu y. >ina!!y* it "ay be '#n'!u e $r#" the stu y that '#"&!e1 !i&i "#!e'u!es* trans$ers#"es* 'an in'rease the trans er"a! $!u1* &r#!#ng the re!ease* an i"&r#ve the site s&e'i$i'ity #$ bi#a'tive "#!e'u!es.

Rea <#re: htt&://in$#r"ahea!th'are.'#"/ #i/abs/10.10B1/DDC-1/00/545B

Trans er"a! Drug De!ivery: 5enetrati#n @nhan'e"ent Te'hniHues

,uth#r: 2ens#n* ;eather A.@. S#urce: Current Drug De!ivery* 9#!u"e /* 8u"ber 1* Fanuary /005 * &&. /3-33+11, (u0lisher: 2entha" S'ien'e 5ub!ishers K &revi#us arti'!e L

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,0stract: There is '#nsi erab!e interest in the s%in as a site #$ rug a&&!i'ati#n b#th $#r !#'a! an syste"i' e$$e't. ;#wever* the s%in* in &arti'u!ar the stratu" '#rneu"* &#ses a $#r"i ab!e barrier t# rug &enetrati#n thereby !i"iting t#&i'a! an trans er"a! bi#avai!abi!ity. S%in &enetrati#n enhan'e"ent te'hniHues have been eve!#&e t# i"&r#ve bi#avai!abi!ity an in'rease the range #$ rugs $#r whi'h t#&i'a! an trans er"a! e!ivery is a viab!e #&ti#n. This review es'ribes enhan'e"ent te'hniHues base #n rug / vehi'!e #&ti"isati#n su'h as rug se!e'ti#n* &r# rugs an i#n-&airs* su&ersaturate rug s#!uti#ns* eute'ti' syste"s* '#"&!e1ati#n* !i&#s#"es* vesi'!es an &arti'!es. @nhan'e"ent via "# i$i'ati#n #$ the stratu" '#rneu" by hy rati#n* 'he"i'a! enhan'ers a'ting #n the stru'ture #$ the stratu" '#rneu" !i&i s an %eratin* &artiti#ning an s#!ubi!ity e$$e'ts are a!s# is'usse . The "e'hanis" #$ a'ti#n #$ &enetrati#n enhan'ers an retar ers an their &#tentia! $#r '!ini'a! a&&!i'ati#n is es'ribe . .eyw#r&s: enhan'er0 retar er0 s%in &enetrati#n0 trans er"a! e!ivery D#cument Type: Review Arti'!e DOI: htt&:// 1. #i.#rg/10./164/1566/0105/66/?15 ,""iliati#ns: 3estern Austra!ian 2i#"e i'a! Resear'h Enstitute* S'h##! #$ 5har"a'y* Curtin )niversity #$ Te'hn#!#gy* 45A 2#1 )1?B6* 5erth* 3estern Austra!ia 6B45. 5ub!i'ati#n ate: Fanuary /005

/ew$ highly e""icient "#rmulati#n #" &icl#"enac "#r the t#pical$ trans&ermal a&ministrati#n in ultra&e"#rma0le &rug carriers$ Trans"ers#mes

4reg#r Cev'a* 4abrie!e 2!u"e

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<e iIinis'he 2i#&hysi%* Te'hnis'he )niversitMt <Nn'hen* Es"aningerstrasse //* D-B1665 <uni'h*

4er"any
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ED@A A4* >ran%$urter Ring 1?3a* D-B0B06 <uni'h* 4er"any

A&en Ar'hive

Abstra't
Trans$ena'* a !#ti#n-!i%e $#r"u!ati#n #$ i'!#$ena'* is es'ribe . Et '#nsists #$ &har"a'euti'a!!y a''e&tab!e ingre ients an "e iates the agent trans&#rt thr#ugh inta't s%in an int# the target tissues. Thera&euti'a!!y "eaning$u! rug '#n'entrati#ns in the target tissue are rea'he even when the a "inistere rug #se in Trans$ena' is be!#w 0.5 "g/%g b# y weight. Trans$ers#"es* $#r" the basis #$ Trans$ena'. These t# 'r#ss the s%in s&#ntane#us!y un er the in$!uen'e #$ )!tra e$#r"ab!e agent 'arriers* 'a!!e Trans$ers#"es are &r#&#se

transe&i er"a! water a'tivity gra ient +see O2i#'hi". 2i#&hys. A'ta 1104 +1??/, //6P,. Di'!#$ena' ass#'iati#n with u!tra e$#r"ab!e 'arriers &er"its it t# have a !#nger e$$e't an t# rea'h 10-ti"es higher '#n'entrati#ns in the tissues un er the s%in in '#"&aris#n with the rug $r#" a '#""er'ia! hy r#ge!. >#r e1a"&!e* Trans$ena' a'hieves intra"us'u!ar agent '#n'entrati#ns between 0.5 an / Qg/g an / an /0 Qg/g at tR1/ h* e&en ing #n the tissue e&th* when it is a "inistere in the #se range 0./5S/ "g/%g #$ rat b# y weight. A "u'h higher rug '#n'entrati#n in a hy r#ge! +1./5S10 "g/%g b# y weight, 'reates the rug !eve! #$ #n!y K0.5 Qg/g in the "us'!e. The rug '#n'entrati#n in the rat &ate!!a $#r these tw# ty&es #$ $#r"u!ati#n is between 1 Qg/g an 5 Qg/g #r 0.4 Qg/g* res&e'tive!y. The re!ative a vantage #$ i'!#$ena' e!ivery by "eans #$ u!tra e$#r"ab!e 'arriers in'reases with the treate rug ass#'iate with 'arriers is '!eare !ess e$$i'ient!y by the "us'!e er"a! thi'%ness an with e'reasing rug #se* as seen in "i'e* rats an &igs0 this 'an be e1&!aine by assu"ing that the 'a&i!!ary &!e1us. En &igs it su$$i'es t# use 0.3 "g #$ i'!#$ena' in high!y e$#r"ab!e vesi'!es &er %g b# y weight* s&rea #ver an area #$ /5 '" /* t# ensure thera&euti' rug '#n'entrati#n in a 5'" thi'% "us'!e s&e'i"en* '#!!e'te un er the agent a&&!i'ati#n site. 3hen the rug is use in a hy r#ge! at B ti"es higher ti"es !#wer an #se* the average intra"us'u!ar '#n'entrati#n is at !east three i'!#$ena' in Trans$ers#"es has the subthera&euti'. This suggests that

&#tentia! t# re&!a'e '#"bine #ra!/t#&i'a! i'!#$ena' a "inistrati#n in hu"ans.

Trans"ers#mes-me&iate& transepi&ermal &elivery impr#ves the regi#-speci"icity an& 0i#l#gical activity #" c#rtic#ster#i&s in viv#1

4reg#r Cev'a*
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4abrie!e 2!u"e * An reas S'hMtI!eina* b

<e iIinis'he 2i#&hysi%* 7!ini%u" r. .E.* Te'hnis'he )niversitMt <Nn'hen* Es"aningerstr. //* D-B1665

<Nn'hen* Deuts'h!an
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ED@A* Enn#vative er"a!e A&&!i%ati#nen 4"b;* >ran%$urter Ring 1?3a* D-B0B06 <Nn'hen* Deuts'h!an

Ch##se an #pti#n t# l#cate9access this article: Che'% i$ y#u have a''ess thr#ugh y#ur !#gin 're entia!s #r y#ur instituti#n Chec' access (urchase 3 55:5

Abstra't
Enn#vative* 'arrier-base sus&ensi#ns #$ severa! '#""#n!y use '#rti'#ster#i s are intr# u'e . These $#r"u!ati#ns '#ntain the re'ent!y su$$i'ient!y 'arrier e!ivery 'an be varie syste"ati'a!!y: eve!#&e agent 'arriers* trans$ers#"es* whi'h are rug e$#r"ab!e t# &enetrate int# #r a'r#ss the inta't s%in barrier. The resu!ting 5. #$ a&&!ie rug is e&#site

e&en ing #n the &re'ise a&&!i'ati#n '#n iti#ns an in the #uter"#st s%in

esign* between 100. an

regi#n. =#w area #se $av#rs the rug retenti#n in the s%in an %ee&s the re!ative area un er the 'urve $#r the b!## '#rres&#n ing &##! be!#w a $ew &er 'ent* at "#st* #$ that resu!ting $r#" the rug rug #se* as we!! as the #se in the b!## . This rug inGe'ti#n. Trans$ers#"es hen'e i"&r#ve the s&e'i$i'ity #$ t#&i'a!

e!ivery an the #vera!! rug sa$ety. En'reasing the t#ta! a&&!ie

&er area* &r#"#tes the syste"i' rug avai!abi!ity. A$ter an e&i'utane#us a&&!i'ati#n #$ su$$i'ient rug a"#unt* thera&euti'a!!y "eaning$u! agent '#n'entrati#n is rea'he n#r"a!!y ha&&ens a$ter the !ag ti"e #$ a&&r#1i"ate!y 4 h t# 6 h. 3hen hy r#'#rtis#ne* e1a"ethas#ne* #r tria"'in#!#ne-a'et#ni e are a "inistere e&i'utane#us!y in trans$ers#"es* $#r e1a"&!e* at the #se #$ 1.5 "g/%g* 1.5 "g/%g* an 1 "g/%g* the res&e'tive '#n'entrati#ns #$ these rugs in the b!## at tRB h are a&&r#1i"ate!y 0.4 Qg/"!* near 0.65 Qg/"! an 0.006 Qg/"!. These resu!ts are '#"&arab!e t# th#se #$ a sub'utane#us inGe'ti#n #$ +3S10T, !#wer a"#unts #$ the sa"e rug. C#n'entrati#n #$ the e&i'utane#us!y a "inistere '#rti'#ster#i s in the b!## is a!ways !#wer than in the s%in* whereas /B Qg/g* 156 Qg/g* an 10 Qg/g are $#un $#r the ab#ve "enti#ne rug #ses at tRB h* res&e'tive!y. Trans$ers#"e-base '#rti'#ster#i s are in the er"ati' bi#!#gi'a!!y a'tive at #ses severa! ti"es !#wer than that 'urrent!y use

$#r"u!ati#ns $#r the treat"ent #$ s%in

iseases. The bi#!#gi'a! anti-e e"a a'tivity #$

trans$ers#"a! '#rti'#ster#i $#r"u!ati#ns hen'e e1'ee s that #$ the '#rres&#n ing '#""er'ia! &r# u'ts* &r#bab!y #wing t# the su&eri#r rug-targeting &#tentia! in the #rgan.

7eyw#r s

Trans$ers#"es0 Trans er"a! e!ivery0 C#rti'#ster#i s0 Regi#-s&e'i$i'ity0 2i#!#gi'a! a'tivity

Review

Drug &elivery acr#ss the s'in

De'e"ber 1??6* 9#!. 6* 8#. 1/ * 5ages 1BB6-1?36 + #i:10.1516/135436B4.6.1/.1BB6, 5D> +646 72, 5D> 5!us +?63 72, Re&rints 5er"issi#ns 4reg#r Cev' <e iIinis'he 2i#&hysi%* 7!ini%u" r. .E.* Te'hnis'he )niversitMt <Nn'hen* Es"aninger Str. //* D-B1665 <Nn'hen* 4er"any

Sin'e the intr# u'ti#n #$ the $irst thr#ugh the s%in +TTS, thera&euti' in 1?B0* a t#ta! #$ 34 TTS &r# u'ts have been "ar%ete an nu"er#us rugs have been teste by "#re than 50 '#""er'ia! #rganisati#ns $#r their suitabi!ity $#r TTS e!ivery. <#st #$ the agents whi'h have been teste have ha !#w "#!e'u!ar weights* ue t# the i"&er"eabi!ity #$ the s%in barrier. This barrier resi es in the #uter"#st s%in !ayer* the stratu" '#rneu". Et is "e'hani'a!* anat#"i'a!* as we!! as 'he"i'a! in nature0 !atera!!y #ver!a&&ing 'e!! "u!ti-!ayers are sea!e by tight!y &a'%e * inter'e!!u!ar* !i&i "u!ti-!a"e!!ae. Che"i'a! s%in &er"eati#n enhan'ers in'rease the trans&#rt a'r#ss the barrier by &art!y s#!ubi!ising #r e1tra'ting the s%in !i&i s an by 'reating hy r#&h#bi' &#res. This is #$ten irritating an n#t a!ways we!!-t#!erate . The TTS a&&r#a'h a!!#ws rugs +K 400 %Da in siIe, t# &er"eate thr#ugh the resu!ting &#res in the s%in* with a sh#rt !ag-ti"e an subseHuent stea y-state &eri# . Drug bi#avai!abi!ity $#r TTS e!ivery is ty&i'a!!y be!#w 50.* av#i ing the $irst &ass e$$e't. 3i er* hy r#&hi!i' 'hanne!s 'an be generate by s%in &#rati#n* with the ai #$ a s"a!! e!e'tri'a! 'urrent +- 0.4 "A/'"/, a'r#ss the s%in +i#nt#&h#resis, #r thera&euti' u!tras#un +$ew 3/'"/0 s#n#&#rati#n,. ;igh-v#!tage +- 150 9* e!e'tr#&#rati#n, wi ens the &#res even "#re an #$ten irreversib!y. These stan ar &#rati#n "eth# s reHuire e1&erien'e an eHui&"ent an are there$#re* n#t &ra'ti'a!0 at best* 'harge /s"a!! "#!e'u!es + 4000 %Da in siIe, 'an be e!ivere e$$i'ient!y a'r#ss the s%in. En s&ite #$ the &#tentia! har" #$ ga get- riven s%in &#rati#n* this "eth# is use t# e!iver "#!e'u!es whi'h '#nventi#na! TTS &at'hes are unab!e t# e!iver* es&e'ia!!y &#!y&e&ti es. =i&i -base rug 'arriers

+!i&#s#"es* ni#s#"es* nan#&arti'!e "i'r#e"u!si#ns* et'., were &r#&#se as a!ternative* !#w-ris% e!ivery vehi'!es. Su'h sus&ensi#ns &r#vi e an i"&r#ve rug reserv#ir #n the s%in* but the aggregates re"ain '#n$ine t# the sur$a'e. C#nventi#na! 'arrier sus&ensi#ns in'rease s%in hy rati#n an /#r behave as s%in &er"eati#n enhan'ers. The re'ent!y eve!#&e 'arriers0 Trans$er#"es* '#"&rise &har"a'euti'a!!ya''e&tab!e* estab!ishe '#"&#un s an are th#ught t# &enetrate the s%in barrier a!#ng the natura!!y #''urring trans'utane#us "#isture gra ient. Trans$ers#"es are be!ieve t# &enetrate the hy r#&hi!i' +virtua!, 'hanne!s in the s%in an wi en the $#r"er a$ter n#n-#''!usive a "inistrati#n. 2#th s"a!! an !arge hy r#&h#bi' an hy r#&hi!i' "#!e'u!es are e!iverab!e a'r#ss the stratu" a$ter '#nGugati#n with Trans$ers#"es. Drug istributi#n a$ter trans er"a! e!ivery &r#bab!y &r#'ee s via the !y"&h. This resu!ts in Huasi-Ier# #r er %ineti's with signi$i'ant syste"i' rug !eve!s rea'he a$ter a !ag-ti"e #$ u& t# a $ew h#urs. The re!ative e$$i'ien'y #$ TTS rug e!ivery with Trans$ers#"es is ty&i'a!!y ab#ve 50 .0 with the a e &#ssibi!ity #$ regi#na! rug targeting.

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;ltra"le8i0le vesicles$ Trans"ers#mes$ have an e8tremely l#w p#re penetrati#n resistance an& transp#rt therapeutic am#unts #" insulin acr#ss the intact mammalian s'in

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Dieter 4ebauera* An reas S'hMtI!einb* 4abrie!e 2!u"eb

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A&en Ar'hive

Abstra't
8ew vehi'!es $#r the n#n-invasive e!ivery #$ agents are intr# u'e . These 'arriers 'an e&en s #n the se!$-regu!ating 'arrier trans&#rt &har"a'#!#gi'a! agents* in'!u ing !arge &#!y&e&ti es* thr#ugh the &er"eabi!ity barriers* su'h as the inta't s%in. This 'a&abi!ity e$#r"abi!ity whi'h e1'ee s that #$ the re!ate but n#t #&ti"iIe !i&i aggregates by severa! #r ers #$ "agnitu e. C#nventi#na! !i&i sus&ensi#ns* su'h as stan ar !i&#s#"es #r "i1e !i&i "i'e!!es* # n#t "e iate a syste"i' bi#!#gi'a! e$$e't u&#n e&i'utane#us a&&!i'ati#ns. En '#ntrast

t# this* the &r#&er!y evise a a&tab!e 'arriers* when a "inistere #n the inta't s%in* trans&#rt thera&euti' a"#unts #$ bi#geni' "#!e'u!es int# the b# y. This &r#'ess 'an be near!y as e$$i'ient as an inGe'ti#n nee !e* as seen $r#" the resu!ts #$ e1&eri"ents in "i'e an hu"ans with the insu!in-'arrying vesi'!es. The 'arrier-"e iate trans'utane#us insu!in e!ivery is un!i%e!y t# inv#!ve shunts* !esi#ns #r #ther ty&es #$ s%in a"age. Rather than this* insu!in is in$erre t# be trans&#rte int# the b# y between the inta't s%in 'e!!s with a bi#-e$$i'ien'y #$ at !east 50. #$ the s.'. #se a'ti#n.

Sur"actant sel"-assem0ly #0<ects as n#vel &rug &elivery vehicles

Ca!u" F Dru""#n Ce!esta >#ng

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Ch##se an #pti#n t# l#cate9access this article: Che'% i$ y#u have a''ess thr#ugh y#ur !#gin 're entia!s #r y#ur instituti#n Chec' access (urchase 3 55:5

Abstra't
The &ast agents $#r he1ag#na!* e'a e has been witness t# a new i"&etus in sur$a'tant se!$-asse"b!y #bGe'ts as rug e!ivery that are an a!ternative t# "i'e!!ar* !a"e!!ar +!i&#s#"e* ni#s#"e an Uinter"e iateV +viI. rh#"b#he ra!* tetrag#na! an "#n#'!ini', an

trans$ers#"e, #r "i'r#e"u!si#n-base vehi'!es. The review $#'us herein is #n the a&&!i'ati#n #$ 'ubi'* =3 +Us&#ngeV, "es#&hases.

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Sur$a'tant se!$-asse"b!y0 Drug e!ivery0 ;e1ag#na!0 Cubi'0 Enter"e iate0 S&#nge

Abbreviati#ns

A><* at#"i' $#r'e "i'r#s'#&y0 A4 336* /-a"in#-3*4- ihy r#-6-"ethy!-4-#1#-5-+4-&yri y!thi#,-HuinaI#!ine ihy r#'h!#ri e0 'ry#-T@<* 'ry#trans"issi#n e!e'tr#n "i'r#s'#&y0 D8A* e#1yrib#nu'!ei' a'i 0 4<A* g!y'ery! "#n##!eate* "#n##!ein0 4<=* g!y'ery! "#n#!in#!eate0 =3* sur$a'tantSwater Us&#ngeV &hase0 W@=S* Huasie!asti' !ight s'attering0 SAXS* s"a!! ang!e X-ray s'attering0 SDS* s# iu" # e'y! su!&hate0 3AXS* wi e ang!e X-ray s'attering

Trans"ers#mes "#r trans&ermal &rug &elivery5

2ens#n ;A. ,uth#r in"#rmati#n

,0stract
Trans$ers#"es +E ea A4, are a $#r" #$ e!asti' #r e$#r"ab!e vesi'!e* whi'h were $irst intr# u'e in the ear!y 1??0s. @!asti'ity is generate by in'#r&#rati#n #$ an e ge a'tivat#r in the !i&i bi!ayer stru'ture. The #rigina! '#"&#siti#n #$ these vesi'!es was s#ya &h#s&hati y! 'h#!ine in'#r&#rating s# iu" 'h#!ate an a s"a!! '#n'entrati#n #$ ethan#!. Trans$ers#"es are a&&!ie in a n#n-#''!u e "eth# t# the s%in an have been sh#wn t# &er"eate thr#ugh the stratu" '#rneu" !i&i !a"e!!ar regi#ns as a resu!t #$ the hy rati#n #r #s"#ti' $#r'e in the s%in. They have been use as rug 'arriers $#r a range #$ s"a!! "#!e'u!es* &e&ti es* &r#teins an va''ines* b#th in vitr# an in viv#. Et has been '!ai"e by E ea A4 that inta't Trans$ers#"es &enetrate thr#ugh the stratu" '#rneu" an the un er!ying viab!e s%in int# the b!## 'ir'u!ati#n. ;#wever* this has n#t been substantiate by #ther resear'h gr#u&s wh# have e1tensive!y &r#be the "e'hanis" #$ &enetrati#n an intera'ti#n #$ e!asti' vesi'!es in the s%in. Stru'tura! 'hanges in the stratu" '#rneu" have been i enti$ie * an inta't e!asti' vesi'!es visua!ise within the stratu" '#rneu" !i&i !a"e!!ar regi#ns* but n# inta't vesi'!es have been as'ertaine in the viab!e tissues. )sing the &rin'i&!e #$ in'#r&#rating an e ge-a'tivat#r agent int# a bi!ayer stru'ture* a nu"ber #$ #ther e!asti' vesi'!e '#"&#siti#ns have been eva!uate . This review es'ribes the resear'h int# the eve!#&"ent an eva!uati#n #$ Trans$ers#"es an e!asti' vesi'!es as t#&i'a! an trans er"a! e!ivery syste"s.
An%it 4u&ta*1 4eeta Aggarwa!*Y*/ Sa"ita Sing!a*/ an Riti%a Ar#ra/
Auth#r in$#r"ati#n Z Arti'!e n#tes Z C#&yright an =i'ense in$#r"ati#n Z

,0stract

Trans"ers#mes: Sel"-Optimi2ing Carriers "#r -i#actives 5DA F 5har" S'i Te'hn#!September/October 2008 62:362-379