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

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

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

Polymer 4

MATERIALS MATERIALS CHARACTERISTICCHARACTERISTIC

Biodegradable PolyesterBiodegradable Polyester

biocompatibilitybiocompatibility nontoxicitynontoxicity processabilityprocessability resorption of degradation productresorption of degradation product

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

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

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

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

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.

Polymer 10

RESULT ANALYSISRESULT ANALYSIS

Morphology of MicrospheresMorphology of Microspheres

In vitro DegradationIn vitro Degradation

Drug ReleaseDrug Release

Storage StabilityStorage Stability

Polymer 11

Morphology of MicrospheresMorphology of Microspheres

Copolymer50m

More denseless porous

Blends20m

Very porous interconnecting

channels

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(%

)

Polymer 13

DSC thermogramsDSC thermograms

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)

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

(%

)

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

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

Polymer 18

Blends of PLLA-PDXOBlends of PLLA-PDXO

easily control easily control

get what you wantget what you want