Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device
-
Upload
laith-welch -
Category
Documents
-
view
27 -
download
0
description
Transcript of Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device
![Page 1: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/1.jpg)
Polymer 1
Poly (L-lacitde)/Poly (1,5-Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in dioxepan-2-one) Blends in
Drug Release DeviceDrug Release Device
Maggie WangMaggie Wang
October 27, 2000October 27, 2000
The main article came from Journal of Polymer Science The main article came from Journal of Polymer Science V38,786,2000V38,786,2000
![Page 2: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/2.jpg)
Polymer 2
CONTENTCONTENT IntroductionIntroduction Gene Therapy Drug Delivery Gene Therapy Drug Delivery
Immunoisolation Device Biodegradable PolyesterImmunoisolation Device Biodegradable Polyester
MaterialsMaterials PLLA, PDXO, Copolymer, Homopolymer BlendsPLLA, PDXO, Copolymer, Homopolymer Blends
Result AnalysisResult Analysis Microshpere Morphology, In vitro degradation, Drug Microshpere Morphology, In vitro degradation, Drug
Release, Storage StabilityRelease, Storage Stability
ConclusionConclusion
![Page 3: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/3.jpg)
Polymer 3
INTRODUCTIONINTRODUCTION Gene TherapyGene Therapy Human gene therapy is defined as a medical intervention based on the alteration of genetic material of living cells in humans.Human gene therapy is defined as a medical intervention based on the alteration of genetic material of living cells in humans.
Drug DeliveryDrug Delivery What’s the big challenge?What’s the big challenge?
two approachestwo approaches Cell Encapsulation---Cell Encapsulation---T.M.S. Chang 1964T.M.S. Chang 1964
What kind of requirement for the device?What kind of requirement for the device?
Biodegradable PolyesterBiodegradable Polyester
![Page 4: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/4.jpg)
Polymer 4
MATERIALS MATERIALS CHARACTERISTICCHARACTERISTIC
Biodegradable PolyesterBiodegradable Polyester
biocompatibilitybiocompatibility nontoxicitynontoxicity processabilityprocessability resorption of degradation productresorption of degradation product
![Page 5: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/5.jpg)
Polymer 5
Biodegradable PolyesterBiodegradable Polyester
The familyThe family
Lactide, glycolide, Lactide, glycolide, -caprolcatone, -caprolcatone,
trimethylene carbonate, etctrimethylene carbonate, etc
Why did they need morphology engineering? Why did they need morphology engineering? Hydrophobicity and semicrystallineHydrophobicity and semicrystalline hard to control degradation ratehard to control degradation rate attachment to drug or proteinattachment to drug or protein
![Page 6: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/6.jpg)
Polymer 6
PLLA- Poly (L-lactide)PLLA- Poly (L-lactide)
SemicrystallineSemicrystalline Tg 55Tg 55CC In Homopolymer, the crystalline domain In Homopolymer, the crystalline domain
show high resistance to degradation show high resistance to degradation
O
O
O
O
ROP *O
O*
O
O
n
Bu2SnO 15h 120°C
![Page 7: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/7.jpg)
Polymer 7
PDXO-Poly (1,5-dioxepan-2-one)PDXO-Poly (1,5-dioxepan-2-one)
Completely amorphousCompletely amorphous high viscous, Tg -39high viscous, Tg -39CC no tendency to crystallize, excellent choice no tendency to crystallize, excellent choice
for the amorphous block in a copolymerfor the amorphous block in a copolymer
ROPO
O
O
O*
n
O
O
Bu2SnO 14h 40°C
![Page 8: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/8.jpg)
Polymer 8
Copolymer P(L-LA-co-DXO)Copolymer P(L-LA-co-DXO)
O
O
O
O
ROP
OO
O
O
O
O
O
c c
O
O
O
stannous-2-ethylhexanoate+
Copolymer is semicrystallineCopolymer is semicrystalline more flexible, moldablemore flexible, moldable consisting soft and hard segments: consisting soft and hard segments: soft phase(DXO) elasticity and the degradation soft phase(DXO) elasticity and the degradation hard phase(LLA) mechanical strengthhard phase(LLA) mechanical strength
![Page 9: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/9.jpg)
Polymer 9
Homopolymerization Blends Homopolymerization Blends PLLA-PDXOPLLA-PDXO
Blends exhibit advantageous Blends exhibit advantageous physical and mechanical propertiesphysical and mechanical properties
phase-separated can obtain double phase-separated can obtain double -layered particles-layered particles
the degradation and release the degradation and release performance can be controlled by performance can be controlled by means of component ratio.means of component ratio.
![Page 10: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/10.jpg)
Polymer 10
RESULT ANALYSISRESULT ANALYSIS
Morphology of MicrospheresMorphology of Microspheres
In vitro DegradationIn vitro Degradation
Drug ReleaseDrug Release
Storage StabilityStorage Stability
![Page 11: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/11.jpg)
Polymer 11
Morphology of MicrospheresMorphology of Microspheres
Copolymer50m
More denseless porous
Blends20m
Very porous interconnecting
channels
![Page 12: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/12.jpg)
Polymer 12
CrystallinityCrystallinity
crystallinity increase as the PLLA ratio increasedcrystallinity increase as the PLLA ratio increased PDXO in the PLLA domains disturb the crystalPDXO in the PLLA domains disturb the crystal
0
10
20
30
40
50
0 20 40 60 80 100
blend content of PLLA (mol% )
Degree o
f crysta
llin
ity(%
)
![Page 13: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/13.jpg)
Polymer 13
DSC thermogramsDSC thermograms
![Page 14: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/14.jpg)
Polymer 14
In vitro degradationIn vitro degradation
In theory,DXO are In theory,DXO are
slower degrading slower degrading
than the L-LAthan the L-LA a high content of L-LA a high content of L-LA
degrade fasterdegrade faster
Copolymer trendencyCopolymer trendency
Blends trendency---L-Blends trendency---L-
LA matrices resistant LA matrices resistant
to water penetrationto water penetration0
20
40
60
80
100
0 50 100 150 200time (days)
Mw
(t)/
MW
(0)
blend(90:10)
blend(70:30)
co (90:10)
co (70:30)
![Page 15: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/15.jpg)
Polymer 15
Drug Release in buffer solutionDrug Release in buffer solution
0
20
40
60
80
100
0 20 40 60 80Time (days)
Rele
ase
of A
M (
%)
blend20:80blend70:30blend90:10PLLA
co70:30co90:10 0
20
40
60
80
100
0 20 40 60 80Time (days)
Rel
ease
of
TM
(%
)
![Page 16: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/16.jpg)
Polymer 16
Storage StabilityStorage Stability
Weight change ---moisture Weight change ---moisture adsorption cause chain cleavageadsorption cause chain cleavage
higher humidity, more decrease of higher humidity, more decrease of MWMW
storage induce crystallizationstorage induce crystallization copolymer appear more sensitive copolymer appear more sensitive
to storage degradationto storage degradation
![Page 17: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/17.jpg)
Polymer 17
CONLUSIONCONLUSIONAnalysis Copolymer Blends PLLA PDXO
Size 50 20
Interface Porous,
channel
Dense, less
porous
Irregular
, cluster
Morphology
crystalline Higher degree
In vitro
Degradation
MW Loss Slower
TM SlowerDrug release
AM Slower
Storage Remain MW more
![Page 18: Poly (L-lacitde)/Poly (1,5-dioxepan-2-one) Blends in Drug Release Device](https://reader036.fdocuments.in/reader036/viewer/2022062718/56812bca550346895d901f22/html5/thumbnails/18.jpg)
Polymer 18
Blends of PLLA-PDXOBlends of PLLA-PDXO
easily control easily control
get what you wantget what you want