ORALI

NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS

(
2018-2019)
ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS

BY
Mr
.VHASALEKETANKULBHUSHAN
B.Phar
m(Fi
nal
Year
)
Mahar
asht
raCol
l
egeofPhar
macy
,
Ni
l
anga–413521
SWAMIRAMANANDTEERTHMARATHWADAUNI
VERSI
TY,
NANDED

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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS
MAHARASHTRACOLLEGEOFPMARMACY,
NILANGA
2018-
2019

Cer
ti
fi
cat
e
Thi
sist
ocer
ti
fyt
hatLi
brar
yAssi
gnmentEnt
it
led

ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS
I
scar
ri
edoutby

MR.VHASALEKETANKULBHUSHAN

Fort
heawar
dofdegr
eei
n

BACHELOROFPHARMACY
Undersuperv
isi
onandgui
dancebyMr.
WAKODES.J.Dept
.Of
Phar
maceuti
cs,
thi
sisfor
war
dedt
oregi
str
ar

S.
R.T.
M.U.Nanded.

Gui
de Pr
inci
pal

Mr
.WAKODES.
J. Dr
.PATI
LS.S.

Dept
.of
Phar
maceut
icsPh.
D.Dept
.of
phar
macol
ogy

M.
C.P.Ni
l
anga M.
C.P.Ni
l
anga

Cer
ti
fi
cat
e
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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS
Thi
sist
ocer
ti
fyt
hatLi
brar
yAssi
gnmentEnt
il
ted

(
ORALI
NSULI
N:AFUTUREOPTI
ONFORDI CS)
ABETI

I
scar
ri
edoutby
BACHELOROFPHARMACY
I
nthepar
ti
alf
ulf
il
lmentof
Bachel
orofPhar
macy
I
nthef
acul
tyofPhar
maceut
ics
wascar
ri
edouti
n
Mahar
asht
raCol
l
egeofPhar
macy
,Ni
l
anga.
Undermysuper
visi
on&Gui
dance.
Mr
.Vhasal
eKet
anKul
bhushan
Undersuper
visi
onandgui
dancebyMr
.WAKODES.J.

.OfPha
Dept r
maceut
ics
t
hisi
sfor
war
dedt
oregi
str
arS.
R.T.
M.U.
Nanded.

Gui
de Pr
inci
pal
Mr
.WAKODES.
J.Dr
.PATI
LS.S.
Dept
.ofPhar
maceut
icsPh.
D.Dept
.of
phar
macol
ogy
M.
C.P.Ni
l
angaM.
C.P.Ni
l
anga

Cer
ti
fi
cat
e
Thi
sist
ocer
ti
fyt
hatLi
brar
yAssi
gnmentEnt
it
il
ed

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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS

(
ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS)

I
scar
ri
edoutby
Mr
.Vhasal
eKet
anKul
bhushan
I
nthepar
ti
alf
ulf
il
lmentof
Bachel
orofphar
macy
i
nthef
acul
tyofPhar
maceut
ics

wascar
ri
edouti
n
Mahar
asht
raCol
l
egeofphar
macy
,Ni
l
anga.
Undermysuper
visi
on&Gui
dance.

Mr
.WAKODES.
J.
Dept
.Of
Phar
maceut
ics
M.
C.P.
Nil
anga

DECLARATI
ON
Iher
ebydecl
aret
hatl
i
brar
yassi
gnmentent
it
led

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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS
(
ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS)

Hasbeenpr
epar
edbymeundert
hegui
dance
andsuper
visi
onofMr
.WAKODES.J.
atMahar
asht
ra
Col
l
ageofPhar
macy
,Ni
l
angai
npar
ti
alf
ulf
il
lmentof
r
equi
rementf
ort
heawar
dofDegr
eei
n

BACHELOROFPHARMACY

If
urt
herdecl
aret
hatIhav
enotsubmitt
edthisassi
gnmentpr
evi
ousl
yfort
he
awardofanydegr
eeordiplomatome.

Pl
ace:
-Ni
l
angaMr
.Vhasal
eKet
anKul
bhushan

Dat
e:-/ /
2019 (
B.phar
m.f
inal
year
)

ACKNOWLEDGEMENT
I
tishumblegraduat
edwithsenseofi
ndebt
edness.It
hankourrespect
ed
andbelovedPri
nci
palDr.
PATILS.S.
SIRM.
C.PNil
anga,f
orhisvaluabl
e
gui
danceandconstantsuppor
twhichl
eadsustowardssuccess.
It
hankourr
espect
edandest
imat
edLect
urer
Mr.WAKODES.J. Dept
.OfPharmaceut
ics,provi
dingmeallnecessary
st
ructur
esfaci
l
iti
essuggesti
onandconstantsupportwhi
chleadstowards
successf
ulcompleti
onoftheli
brar
yassi
gnmentwor kapartf
rom hisrouti
ne
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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS
depar
tmentandacademi
cschedul
eencouragi
ngproj
ectworkisr
eal
l
y
ast
onishi
ngforwhi
chweshallev
erremaingr
atef
ultohim.
Iam extremelygreatertomybel ovedlect
urersDr.Pati
lS.
S
Dr.
C.MJangmeMr .GaradS. P.Dr .
SonawaneL.V.Mr.TarangeG.M.
Mr
.HanpudeS. U.Mrs.TagarkhedeA. B.Mr
.UsnaleS.V.Mr.MoreR.R.Mr
.
AuteA.A.Mr.Shet
karM.A.Mr .PanchalC.
V.Mr .
KumbharS. P.Mr.
GhodkeA.Y.Mr.
PhadR. P.Mr .WakodeS.J.Miss.
BhalkeN.B.
It
akepleasurei
nthankingMr .
PaulGajananBALAJI.
complet
ingof
l
i
braryassi
gnmentwi t
hintime.Myspecialthankst
oallB.Phar
macy.
Student
sf orhel
pingmeinassi gnment
.
Iconsi
deroursel
fpr
ivi
l
eget
ohav
eseensuchanent
it
yinourpar
ent
s.
Mr
.vhasal
eket
ankul
bhushan

(
B.Phar
m.Fi
nal
Year
)

THEASSI
GNMENTWORK.
 Ti
tl
eoft
heassi
gnment:
-ORALI
NSULI
NAFUTUREOPTI
ONFORDI
ABETI
CS

Wor
kcar
ri
edat:
-Mahar
asht
racol
l
egeofphar
macy

Nameoft
hest
udent:
-Mr
.VHASALEKETANKULBHUSHAN

Rol
lNo :
-66
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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS

Li
brar
yassignmentsubmit
tedf
ort
hepar t
ialful
fi
ll
mentforB.phar
m Degr
ee
undersuper
vi onofMr
si .WakodeS.J.Dept.ofPhar
maceuti
cs.

Nameoft
hei
nst
it
ute :
-Mahar
asht
raCol
l
egeOfPhar
macy
,
Ni
l
anga.

Year :
- 2018-
2019

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 ORALI
NSULI
N:AFUTUREOPTI
ONFORDI
ABETI
CS

I
ndex
Sr
.No. Cont
ent PageNo.

1 Abst
ract 9

2 I
ntr
oduct
ion 9

3 Mat
eri
als 10

4 11
BENEFI
TSAndOBSTACLESORALI
NSULI
N
DELI
VERY

5 12
NOVELSTRATEGI
ESFORORALI
NSULI
NDELI
VERY

6 Pol
ymer
sut
il
izedf
orpr
epar
ati
onofpol
ymer
icNPs 15

7 FUTURETRENDSFORI
NSULI
NDELI
VERY 17

SYSTEMS

8 CONCLUSI
ON AndREFERENCE
19

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ABETI
CS

1.
ABSTRACT
Insul in-
loaded pol ymermi cropar ti
cles (ILP)composed ofcr ossl i
nked
pol y(met hacr ylicaci d)andpol y(ethyl
enegl y col)ar emul t i
-funct ional
car ri
er s showi ng hi gh insul ini ncorporation ef ficiency ,a r api di nsul i
n
release i nt he i ntestine based on t heirpH- dependentcompl exat i
on
pr oper t
ies,
enzy me- inhibiti
ngef fectsandmucoadhesi vechar acter isti
cs.Thus,t hey
ar epot ent ialcarriersf ori
nsul indel i
veryviaanor al route.Recentst udi es
suggestt hatt hepol ymercomposi t
ionandpar ticlesi zeofI LPst rongly
i
nf luencedi nsulinbioav ai
lability.Therefore, thepr esentst udyai medat
finding an opt i
malf ormul ation and desi gning car r
iersf oror ali nsul i
n
del iveryusi ngi nv ivoexper i
ment s.Varioust ypesofI LPswer epr epar ed
and
admi nister edor al l
yt oheal thyandt y pe1and2di abet icr ats.Themost
pr omi singf ormul ati
onwassubsequent l
yusedf ori nv ivomul t
ipl eor al
admi nistrat i
on st udies usi ng di abetic r ats. The mi cropar t
icles of
diamet er s of<53 Am ( SS- I
LP)composed ofa 1: 1 mol arr atio of
met hacr ylic
aci d/et hy lenegl ycoluni t
sshowedt hemostpr onouncedhy pogl ycaemi c
ef fectsf ollowingor aladmi nistrationtoheal thyrat s,achi evinga9. 5%
phar macol ogicalav ailabi
li
tycompar edt osubcut aneousi nsul ininj ection.
Thei rusef ulnesswasal soconf irmedwi thbot hty pe1and2di abet icr at
gr oups.I namul t
ipleadmi nist rati
onst udy,SS- ILPsi gnificant lysuppr essed
thepost prandi alriseinbloodgl ucoseandshowedcont inuous
hy pogl ycaemi cef f
ectsf oll
owi ng3t imes/ dayor aladmi nistrationt obot h

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ABETI
CS
diabeti
cratgroupsi nt hepresenceoffoods.Theseresult
sindicat
ethat
the
bloodglucosel evel
sofdi abeti
cratscanbeeffecti
vel
ycontrol
ledbyoral
SS-ILPadmi ni
strati
on,andthusSS-ILPwoul
dbeapr omisingdel
ivery
carri
erofinsul
inv i
at heoralr
oute.

2.I
NTRODUCTI
ON
Ov erthepastsev er al decades, biotechnol ogyhasdev eloped
extensi velyandl edt oasi gnificanti ncr easei nt henumberof
bioengi neer edpr oduct s.Thepr ogr essoft hesef ieldshashada
greati mpactont het her apeut i
cagent susedt ot reatmany
diseases, suchasdi abet es, et c., whi char eof tendi ffi
culttot reat
withcur rentmedi ci nes.Mostoft hesepr oduct sar epept i
des
andpr oteins, whi char egener al l
yadmi nisteredv iat he
par enteral rout e.Howev er,or al admi ni strati
oni st hemost
desi r
abl er out ef ort aki ngt hesedr ugsbecauseofeaseof
admi nist ration, thusr esul t
ingi ngoodpat ientcompl iance.
Insulinr emai nst hemostef f
ect ivedr ugf oradi abet i
cpat ient
tocont r
ol t
hei rbl oodgl ucosel ev els.Ther outef orinsul i
n
deliveryi sr est ri
ct edt osubcut aneousi nject i
ons, asopposedt o
theor al rout e, duet oi nsul ininact ivat i
onbypr ot eol ytic
enzy mesi nt hegast roint estinal tractandl owper meabi lit
y
throught hei ntest inal membr ane[ 1,2] .Howev er, t
hesubcut aneous
i
nject i
onofi nsul inhasv ariousdi sadv antagessuchas
hyper i
nsul i
nemi a, pai n, allergicr eact ionsandl owpat ient
compl i
ance.Anot heri mpor t
anti ssuewi t
hi nsul i
ni st hat
par enteral admi nist rationdoesnotr epl i
cat ethenor mal
dynami csofendogenousi nsul inr elease, resul t
ingi naf ail
ur e
toachi ev eal ast i
nggl ycaemi ccont r
ol inpat i
ent s

3.Mater
ial
s
.
1.Met
hacry
li
caci
d
Methacryl
i
c aci
d( MAA),dimethoxy pr
opylacet
ophenone(
DMPA) and
st
reptozot
oci
nwereobt
ainedf
rom Sigma-
Aldr
ich
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ONFORDI
ABETI
CS
Co.( St.Loui s,MO, USA) .Tetraethyleneglycol di
met hacryl
ate
(TEGDMA)andpol y (
ethy l
enegl ycol)monomet hylether
monomet hacr yl
ate( PEGMA, wit
hnomi nalPEGmol ecular
wei ghtof1000, cor respondi ngto23r epeati
nguni ts)wer e
pur chasedf rom Pol ysciencesInc
2.Insul ini ncor porat i
on
Insul ini ncor porationwasper f
ormedbyequi libri
um
par titi
oni ngi ntocompl exati
onhy dr ogel
sasdescr ibedpr evi
ousl
y
.Br iefly, crystall
inehumani nsuli
n( 10mg)was
dissol v edi n200ALof0. 1M HCl .Thei nsul
insol utionwas
dil
ut edwi t
h19. 6mLofphosphat e-
buf f
eredsal i
ne( PBS,
pH=7. 4)andpHwasadj ustedto7. 4wi th200ALof0. 1M
NaOH.Loadi ngwasaccompl i
shedbyi mbibi
ng140mgof
driedmi cropar ti
clesf or2hi nthei nsuli
nsolut i
on.The
par ticleswer ecollapsedwi th20mLof0. 1M HCl and
fil
ter edusi ngcel luloseacet ate/cellul
osenitratef i
lterpaper
with1. 0Am por es.

4.
BENEFI
TSOFANORALI
NSULI
NDELI
VERY

1) Pat i
entcompl i
ance
2) Conv enient
3) Painless
4) Easyf orself-
medicat
ion
5) Av oi
dwei ghtgain
6) Reduces t he danger of hypogl
ycemi
cincident
s,
immuner esponsesandot herpr
obl
emsassoci
atedwit
h
SCroute
7) Costef fect
ive

 OBSTACLESTOORALI
NSULI
NDELI
VERY
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CS
1.Absor
pti
ont
hroughgast
roi
ntest
inalmembr
ane
Paracel
lularandt hetranscell
ularroutei
sthegeneralr
outef orabsor
pti
onof
molecules.Theear li
eronei sfavoredpathforthosehydrophili
cmolecul
es
which hav e a mol .Wt .less than 500 Da.The mol ecules havi
ng hi
gh
molecularwei ghtli
kei nsuli
n( about6KDa)woul dnotent erviathi
sroute.
Absorpti
on ofi nsuli
n by t ranscel
lul
arroutei s hi
ndered by enormous
molecularsize,i
tschar ge,anditshydrophi
l
ici
ty

2.Enzy
mespr
esental
lov
eri
nGI
T
Thereisagr oupofaspar ti
cpr oteasesstatedt oaspepsi nispresentwithi
n
thestomach.Pancr eaticpr oteasespresenti nsmallintest
inecompr isi
ng
the serine endopept i
dase ( tr
ypsi
n, α- chymotry
psin, elastase and
exopepti
dases,carboxy peptidase A,and car boxy
peptidase B)r esul
tsin
degradat
ion ofpr oteins.Var i
ous otherenzy mes ar e sit
uated att he
brush–bordermembr ane ori nt heent erocytes ofthe intesti
naltract.
Foll
owingi stheor derofenzy mati
cdegr adat i
onofi nsuli
ni nt hesmal l
i
ntesti
ne:Duodenum >j ejunum >i l
eum
3.
Stabi
li
tyofi
nsul
in
Thest ruct
ureofinsuli
nisv erydel i
cate.Stabili
tyi saf f
ectedbycomponent
element sinaddit
iontopr ocessi
ngel ement s.Sev eralprotTeindegr adation
pathway s ar e oxidation, phot odegradation, di sulfi
de scr ambl i
ng,
deami dati
on,aggregati
on,pr eci
pi t
ati
on,di ssoci ati
on,and f ragment ati
on.
Insuli
nispronetooxidati
vedamaget hroughr eact i
onofcer t
ainami noaci ds
withoxy genradical
spr esenti nt hei
renv ir
onment .Oxidationcanal tera
protei
n’s phy si
ochemical char acteri
stics ( e.g.,f olding and subuni t
associati
on)andleadtoaggr egationorf r
agment ation.Met hionine,
cy stei
ne,
histi
dine,t
rypt
ophan,andt yr
osinear emostl iablet ooxidation.
5.
NOVELSTRATEGI
ESFORORALI
NSULI
NDELI
VERY
 Nanopar
ti
cles(
NPs)
ANPi
sasmal
lent
it
ythatwor
ksasanent
ir
euni
tinr
elat
ionwi
tht
ranspor
t

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 ORALI
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CS
andotheraspects.Par t
icl
esizeofNPsr angesf rom 10t o1000nm.Mor e
att
enti
onhasbeenf ocusedonNPsbecauset heyi ncreasetheabsorpt
ionof
adrugduet onano-sizedparti
cl
eandgr eat ersur f
acear ea.
[21]Furt
her
mor e,
i
tcant riggeraswel lascontrolther eleaseoft hecont entwhichmay
enhancethetransmucosalt r
ansportandcel l
ularuptake.Targeti
ngwillal
so
bepossiblewhenattachedt oasuit
ablemoi ety. ]

 Pol
ymer
icNPs
Biocompatibl
eandbi odegr
adablepoly
mer icNPshavet urnedouttobean
i
dealcar r
ierfordel i
veri
ngpr ot
einsandpept i
desor al
l
y .Itimpr
ovesor al
i
nsulinbioavail
abil
i
tyasi tsuppli
esast eadyenvi
ronmentf ortheencased
drug.[
2]PolymericNPsar eclassi
fiedi
ntotwotypes.Nanospheresinwhich
drugisdistri
butedint hepolymermatrix,andnanocapsulesinwhichdrug
coreisenclosedbyapol ymericfi
lm.
 Sol i
dlipidnanopar ti
cles
Oneoft heimpor tantcol l
oidalcarri
ersisSLNs,composedofphy siological
l
ipid,usual lydispersedinanaqueoussur f
act antsoluti
on.SLNof f
erssome
adv antagesl ikenanosi zer angeandcompar ativel
ynarrowsizedistri
bution,
cont rol
ledr eleaseofdr ugov eral ongper i
odoft i
me,protect
ionofdr ug
agai nstchemi caldegradation,nontoxic,relativelycheaperandst abl
e,can
beeasi lyf r
eezeorspr aydr i
ed.Sarment oetal .havereport
edinsuli
n-l
oaded
SLNscoat edwi t
hchitosanwhi chshowedbenef it
sofmucoadhesi veand
absor ption enhanci ng pr operti
es ensur i
ng si gni
fi
cantl
yl owered bl ood
glucoseupt o24h.Thechemi caldegradati
onofi nsuli
ninGITwasav oided
by sol id mat r
ix ofSLN wher eas intesti
nalabsor pti
on ofinsulin was
enhancedbychi tosancoat ing
 Li
posomes
Li
posomesar esmallconcentri
cbilayervesicl
esthatcanbef or
medf r
om
cholest
erolandnontoxicphospholipids.Li
posomesof f
ersev er
al
advantagesli
kenanosize,abletoincorporatebothhy drophi
li
cand
hydrophobi
cdr ug,i
mpr ov
edef fect
ivenessandt herapeuti
cindexofthedrug,
bett
erstabil
it
ybyencapsul at
ion,non-hazardous,compat ibl
einbiol
ogical
envi
ronment ,
biodegradable,
andnonant i
genic.Li
posomesar ecl
assif
ied
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CS
accordi
ngtothesi
zeandnumberofbi
l
ayer
sasuni l
amel
larv
esicl
es(lar
ge
unil
amell
arvesi
cl
esandsmall
unil
amell
arv
esi
cles)andmult
il
amellar
vesi
cles
 SNEDDSs
SNEDDSs ar ethermody namicall
y stable and isotr
opic mixture ofoi l
,
surf
actant,andcosur fact antandwhenmi xedwi thwat er,i
twi l
linstantly
for
m anO/ W nanoemul sionwithar angeof50nm.Thi snanosizeishel pful
i
nef fi
cientabsorptionoft heoildroplet
s.[
32]Thisi sapr econcentr
at eor
anhydrousf orm oft henanoemul sion which can bedi spensed in hard
gel
atincapsules.Dissolutionofpoor l
ywatersol
ubledr ugscanbei ncreased
usi
ngSNEDDSl eadingt ot hedevel
opmentofsol ubil
izedphasesf r
om whi ch
absorpti
onmi ghttakepl ace.
 Mi
cel
les
Thecor eofmi cell
esconsi stsMi cel
lesaresel f-assembl edtonanosi zed
aggregat esf ormedbyofhy drophobicmoi etywher eascor onaconsi st sof
hydrophilicmoi ety.Endocy tosisisthecommonmechani sm fordeliveryof
i
nsulinthr oughmi cel l
es,andt hisisaf f
ectedbysur facepr operti
esof
nanocar ri
ers.Thegl ucoser esponsivemi cellesar edev el
opedbyt he
compl exat i
onofapheny lboronicacid-containingbl ockcopol ymer( e.g.,
poly
[-
ethyl
enegl ycol ]
-b-poly[asparticacid-co-aspar tamidopheny lbor onicacid])
andagl y copol ymer( e.
g.,poly[asparticacidco- aspar t
glucosami ne]).This
compl exof fersomeadv antagessuchasf ormat ionofclumpcanbe
eli
minatedbecauseoft hepol y(ethylenegl y
col )shell,
increasedsensi t
ivi
ty
tothegl ucosel evel,andf astresponset ochangei nglucoseconcent rati
on
atthephy si
ol ogical pH
 NGs
NGsar enanosizedparticl
esobt ainedbycr oss-
li
nkingpolymer
icnetwor
ks
thatswellinagoodsol vent.Nanogel sareusuall
y10t o100nm indiameter
.
C.Feng, andX.Chenetal .reportedt heprepar
ati
onofCMCS
(carboxymethylchit
osan)/CS( chitosan)nanosgelofinsul
i
nusingthe
simpleionicgel
ationmet hod.Sol uti
onsofCMCS

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6.
Pol
ymer
sut
il
izedf
orpr
epar
ati
onofpol
ymer
icNPs

Pol
ymer Met hodof Descr
ipt
ion
preparati
on
PLGA Mul t
ipleemulsions, Ali
phat i
cpol yester.
solventevaporati
on Bloodgl ucosel evel
technique decreasesf orupt o
24h.Compl exati
on
withsodi um lauryl
sulf
at efacil
itates
l
oadingef f
iciencyof
i
nsulin.Encapsul ati
on
effi
ciencyofi nsuli
n
reachedupt o90%

PLA(
pol
yl
act
ides) Sol
ventev
apor
ati
on Mor
ehy
drophobi
c

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t
echni
que thanPLGA.Duet oits
crystall
inenat ure,it
degradesmor eslowly
PCL Doubl eemul si
on Polyesterpol ymer .It
met hod hasv iscoel ast i
c
proper t
iesand
possesseseasy
formabi li
ty.
Gener atingl essaci di
c
environmentdur ing
degradat ion
Pol
y(acr
yli
caci
d) Compl ex Nondegr adabl e
coacer vati
onmet hod polymer swi th
mucoadhesi v e
proper t
iesbasedon
acryli
cormet hacryl
ic
acid.Excel lent
bindingef f
iciencyon
muci nandshowspH
dependentr eleaseof
drug
Dext
ran Prepar edby Dextransul fateisan
polyelectrol
y te exocel l
ularbact eri
al
compl exat i
onof polysacchar ide.Itis
opposi tel
ychar ged pHsensi tive.Vi t
ami n
natural polymers B12coat edNPi s
usedasacar r
ierfor
theor aldel i
v eryof
i
nsul i
n
Al
ginat
e Ionotropicpr e Polysacchar ide
gelati
onf ollowedby obt ainedf r
om mar i
ne
polyelectrol
y te brownal gae.I tisnon
compl exat i
on toxicand
biodegr adabl e
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poly mer
Chit
osan I
onot
ropicgelati
on Weakpol ybase.
wi
thtr
ipolyphosphat
e Av ailabl
ei nhighand
lowmol ecul arwei
ght
chitosan.HPMCP
coat edchi tosanNP
prot ectsinsulinf
rom
har shGI T
HPMCP: Hydroxy
propyl
methy
lcell
ulosephthal
ate,GI T:
Gastroint
esti
nalt
ract,
PLGA:Polylacti
ccoglycolicaci d,PCL: Pol
yɛ
caprolact
one

7.
FUTURETRENDSFORI
NSULI
NDELI
VERY
SYSTEMS

I sl
etcell
t r
anspl antation
Thisi sar ecent l
y dev eloped surgicalpr ocedur e cal
led t he Edmont on
prot
ocol-wher ebyi sletcellsfrom adonat edhumanpancr easar einject
ed
i
nto
theliverofar eci
pi entwi tht y
pe1di abetes.transplantedcel l
sbegi nto
secr
etei nsul
in,whi l
et he r ecipi
entneeds t ot ake immunosuppr essive
medicati
onsforl i
fet opr ev entrej
ect
ionoft hetr
anspl antedt issue.Clini
cal
tr
ial
scont i
nuet oest abli
sht hesafet
yandl ong-t erm effecti
v enessoft his
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pr
ocedur
easameansofsuppl
yi
ngi
nsul
i
n

I
nsul
innanopump

Thenanopumpi sapower f
uldeviceandhasmanypossi bleappl
i
cationsin
themedi calfield.Thefirstappli
cati
onoft hepump, i
ntr
oducedbyDebi ot
ech,
i
sI nsuli
ndeliver y.Thepumpi njectsInsuli
ntothepati
ent'
sbodyina
constantrate,balancingt heamountofsugar sinhisorherbl
ood.Thepump
canal administersmal ldrugdosesov er

 Genet herapy
Twor ecentreportsdescri
ber esearchint
ogenet herapyfordi
ff
erent
aspectsofdiabetes.Theser eportsareintheforef
rontofwhatwillnodoubt
beongoingandexci ti
ngresear charisi
ngfr
om t hedecodi
ngofthehuman
genome.Sci enti
stshaveidentifi
edagenecal ledSHIP2thatappearsto
regul
ateinsuli
n.Suchf i
ndingsmake
SHIP2apot entialgenetherapytargetforthe

treat
mentoft y
pe2di abet
esaimedati mpr ovi
ngtheindi
v i
dualinsuli
n
regulat
ion.Apr otei
nthatbl
ockstheov ergrowthofbloodv essel
si ntheey e
i
sbei ngstudiedaspossibl
egenet herapyf ordiabet
icret
inopathy.Ar ecent
studyshowedt hattr
eatmentwiththepr otein,
call
edpigmentepi thel
ium-
deriv
edf actor,orPEDF,pr
eventedexcessi venewbl oodvesselformat i
onin
anani mal model ofr
eti
nopathy
.Itmayal sobeusedt otreatmacul ar
degeneration
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8.CONCLUSI ON
Theadv ancesmadei ninsul indeli
verycoul dsurelyprov idei ntensiveinsuli
n
therapyr egi
menst hatcanr educethemul ti
pledailysubcut aneousi nj
ections
andheav yburdenofcompl i
anceonpat i
ents.Thereforepr efer
encer esearch
andi nvesti
gati
onmustgoont hedev elopmentofmor esaf eandef f
ective
deliveryofinsuli
n.Thedev elopmentofdr ugdeli
verysy st emsf orprotei
ns
continuest obepur suedact ivel
yinacademi candi ndust ryci r
cles.The
successofcommer cial
t echnologiesandt heemer genceofnewoneswi l
l
bedemonst ratedonl ywit htime.Anor aldeli
verysy st
em ofi nsulinwillhave
tremendousbenef i
tsi nter msofdecr easednumberofi nject i
onsf or
diabet i
cpatientsandar educedi ncidencesi de
effects.
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REFERNCES
1.Al -Tabakha, M.M.andA. I.Ar i
da, Recent
chal l
engesi ninsul i
ndel i
ver ysy stems: Areview.
IndianJ.Phar m.Sci .
,70: 278- 86.( 2008)
2.Di abet esmel l
it
us, I
nformat ionAv ai
labl
ef orm:
www.Sy stem: A12- weekpr oof -of-
conceptt rial
i
npat ient swi kipedia.org, accessdat e:
23/ 01/ 2009
3.Agar wal ,V., andKhan, M. A., Currentstatusof
theor aldel i
ver yofinsulin.Phar m.Tech. ,
25
(10) :76- 90( 2001)
4.Ber ger onJ. J.,“
Pol ypeptideHor moneRecept ors
InVi vo: Demonst rati
onofI nsul i
nBi ndingto
Adr enal Gl andandGast roint estinalEpitheli
um
byQuant itati
veRadi oautogr aphy ”J.Hi
, st
ochem.
Cy tochem. 28, 824–835( 1980) .
5.Pi l
lionD. J.,Ganapat hyV. ,andLei bachF.H. ,
“Ident i
ficat i
onofI nsul i
nRecept ors

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