2. Polymer1 Poly (L-lacitde)/Poly (1,5- dioxepan-2-one) Blends in Drug Release Device Maggie Wang October 27, 2000 The main article came from Journal of Polymer Science V38,786,2000

3. Polymer2CONTENT n Introduction Gene Therapy Drug Delivery Gene Therapy Drug Delivery Immunoisolation Device Biodegradable Polyester Immunoisolation Device Biodegradable Polyester n Materials PLLA, PDXO, Copolymer, Homopolymer Blends PLLA, PDXO, Copolymer, Homopolymer Blends n Result Analysis Microshpere Morphology, In vitro degradation, Drug Release, Storage Stability Microshpere Morphology, In vitro degradation, Drug Release, Storage Stability n Conclusion

4. Polymer3INTRODUCTION Gene Therapy Gene 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 Delivery What’s the big challenge? What’s the big challenge? two approaches two approaches  Cell Encapsulation--- T.M.S. Chang 1964 What kind of requirement for the device? What kind of requirement for the device?, Biodegradable Polyester

5. Polymer4 MATERIALS CHARACTERISTIC Biodegradable Polyester  biocompatibility  nontoxicity  processability  resorption of degradation product

6. Polymer5 Biodegradable Polyester The family Lactide, glycolide,  -caprolcatone, trimethylene carbonate, etc Why did they need morphology engineering? n Hydrophobicity and semicrystalline n hard to control degradation rate n attachment to drug or protein

7. Polymer6 PLLA- Poly (L-lactide) n Semicrystalline n Tg 55  C n In Homopolymer, the crystalline domain show high resistance to degradation Bu 2 SnO 15h 120°C

8. Polymer7 PDXO-Poly (1,5-dioxepan-2-one) n Completely amorphous n high viscous, Tg -39  C n no tendency to crystallize, excellent choice for the amorphous block in a copolymer Bu 2 SnO 14h 40°C

9. Polymer8 Copolymer P(L-LA-co-DXO) n Copolymer is semicrystalline n more flexible, moldable n consisting soft and hard segments: soft phase(DXO) elasticity and the degradation hard phase(LLA) mechanical strength

10. Polymer9 Homopolymerization Blends PLLA-PDXO n Blends exhibit advantageous physical and mechanical properties n phase-separated can obtain double - layered particles n the degradation and release performance can be controlled by means of component ratio.

11. Polymer10 RESULT ANALYSIS n Morphology of Microspheres n In vitro Degradation n Drug Release n Storage Stability

12. Polymer11 Morphology of Microspheres Copolymer 50  m More dense less porous Blends 20  m Very porous interconnecting channels

13. Polymer12Crystallinity n crystallinity increase as the PLLA ratio increased n PDXO in the PLLA domains disturb the crystal

14. Polymer13 DSC thermograms

15. Polymer14 In vitro degradation n In theory,DXO are slower degrading than the L-LA n a high content of L-LA degrade faster n Copolymer trendency n Blends trendency---L-LA matrices resistant to water penetration

16. Polymer15 Drug Release in buffer solution

17. Polymer16 Storage Stability n Weight change ---moisture adsorption cause chain cleavage n higher humidity, more decrease of MW n storage induce crystallization n copolymer appear more sensitive to storage degradation

18. Polymer17 CONLUSION

19. Polymer18 Blends of PLLA-PDXO easily control get what you want