傳統上，PLGA作為藥物載體大多應用於長效釋放，其釋放機制主要為PLGA微粒水解後的藥物釋放。然而在癌症的治療上，常常需要於短時間快速大量的釋放抗癌藥物於癌症患部，使癌細胞大量快速死亡，故傳統劑型無法達此要求。本研究提出一可快速釋放的藥物載體系統。我們將PLGA利用雙乳化製備方法包覆碳酸氫鈉和抗癌藥物Doxorubicin，利用碳酸氫鈉對於酸性環境會產生二氧化碳的特性，在endosome內產生二氧化碳來破壞殼層結構並釋放抗癌藥物Doxorubicin，作為能在短時間內釋放的劑型。實驗分為三大部分，第一部分為利用雙乳化製備方法，製備出PLGA微粒，探討不同碳酸氫鈉比例對於PLGA微粒型態的影響，找出最適化的製備參數。第二部分則是檢驗包覆碳酸氫鈉的PLGA微粒放置於不同酸性環境下，探討Doxorubicin的釋放曲線；同時也利用場發式掃描式電子顯微鏡觀察PLGA微粒表面型態的改變。第三部份是將人類肝癌細胞(Hep 3B)作為細胞測試的模型，將PLGA微粒與細胞共培養後，利用共軛焦螢光顯微鏡來觀察細胞核是否會呈現紅色螢光以驗證Doxorubicin的釋放。此外也利用細胞活性測試(MTT Assay)來驗證PLGA微粒具有毒殺肝癌細胞的能力。由以上三部分的實驗可驗證我們所製備的PLGA微粒具有攜帶藥物與毒殺肝癌細胞的能力，而釋放時間也比傳統PLGA微粒來的快，因此具備作為短時間釋放劑型的潛力。

1. Northfelt, D.W., et al., Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma. J Clin Pharmacol, 1996. 36(1): p. 55-63.
2. Xiao, W., et al., Co-delivery of doxorubicin and plasmid by a novel FGFR-mediated cationic liposome. Int J Pharm, 2010. 393(1-2): p. 119-26.
3. Angioli, R., et al., Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies. Int J Gynecol Cancer, 2007. 17(1): p. 88-93.
4. Poirier, V.J., et al., Liposome-encapsulated doxorubicin (Doxil) and doxorubicin in the treatment of vaccine-associated sarcoma in cats. J Vet Intern Med, 2002. 16(6): p. 726-31.
5. Oja, C., et al., Doxorubicin entrapped within liposome-associated antigens results in a selective inhibition of the antibody response to the linked antigen. Biochimica Et Biophysica Acta, 2000. 1468(1-2): p. 31-40.
6. Shinozawa, S., Y. Araki, and T. Oda, Tissue distribution and antitumor effect of liposome-entrapped doxorubicin (adriamycin) in Ehrlich solid tumor-bearing mouse. Acta Med Okayama, 1981. 35(6): p. 395-405.
7. Forssen, E.A. and Z.A. Tokes, Attenuation of dermal toxicity of doxorubicin by liposome encapsulation. Cancer Treat Rep, 1983. 67(5): p. 481-4.
8. Gabizon, A., A. Meshorer, and Y. Barenholz, Comparative long-term study of the toxicities of free and liposome-associated doxorubicin in mice after intravenous administration. J Natl Cancer Inst, 1986. 77(2): p. 459-69.
9. Mayhew, E.G., et al., Effects of liposome-entrapped doxorubicin on liver metastases of mouse colon carcinomas 26 and 38. J Natl Cancer Inst, 1987. 78(4): p. 707-13.
10. Storm, G., et al., Potential pitfalls in in vitro antitumor activity testing of free and liposome-entrapped doxorubicin. J Pharm Sci, 1988. 77(10): p. 823-30.

11. Khang, G., et al., Fabrication of tubular porous PLGA scaffold by emulsion freeze-drying method. Polymer-Korea, 1999. 23(3): p. 471-477.
12. Jalil, R. and J.R. Nixon, Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties. J Microencapsul, 1990. 7(3): p. 297-325.
13. Heller, J., Controlled drug release from poly(ortho esters). Ann N Y Acad Sci, 1985. 446: p. 51-66.
14. Heller, J., Controlled Release of Biologically-Active Compounds from Bioerodible Polymers. Biomaterials, 1980. 1(1): p. 51-57.
15. Dixit, V., et al., Functional characteristics of primary rat hepatocytes in monolayers and on three-dimensional PLGA scaffold. Gastroenterology, 1999. 116(4): p. A1204-A1204.
16. Oh, J.H., In vivo comparison of corneal substitutes using PLGA scaffold, Type I collagen film, Type I collagen film combined with amniotic membrane and lyophilized homologous cornea. Investigative Ophthalmology & Visual Science, 2002. 43: p. U1190-U1190.
17. Astete, C.E. and C.M. Sabliov, Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed, 2006. 17(3): p. 247-89.
18. Kitchell, J.P. and D.L. Wise, Poly(lactic/glycolic acid) biodegradable drug-polymer matrix systems. Methods Enzymol, 1985. 112: p. 436-48.
19. Cohen, S., M.J. Alonso, and R. Langer, Novel approaches to controlled-release antigen delivery. Int J Technol Assess Health Care, 1994. 10(1): p. 121-30.
20. Zwelling, L.A., et al., Protein-associated deoxyribonucleic acid strand breaks in L1210 cells treated with the deoxyribonucleic acid intercalating agents 4'-(9-acridinylamino) methanesulfon-m-anisidide and adriamycin. Biochemistry, 1981. 20(23): p. 6553-63.
21. Nelson, E.M., K.M. Tewey, and L.F. Liu, Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A, 1984. 81(5): p. 1361-5.

22. Janes, K.A., et al., Chitosan nanoparticles as delivery systems for doxorubicin. Journal of Controlled Release, 2001. 73(2-3): p. 255-267.
23. Wang, Z., Effects of the Process Parameters on the Initial Burst Release of Poly(lactide-co-glycolide) Microspheres Containing Bovine Serum Albumin by the Double-Emulsion Solvent Evaporation/Extraction Method. Journal of Applied Polymer Science, 2010. 115(5): p. 2599-2608.
24. Jeffery, H., S.S. Davis, and D.T. Ohagan, The Preparation and Characterization of Poly(Lactide-Co-Glycolide) Microparticles .1. Oil-in-Water Emulsion Solvent Evaporation. International Journal of Pharmaceutics, 1991. 77(2-3): p. 169-175.
25. Li, Z., et al., Bovine Serum Albumin Loaded Solid Lipid Nanoparticles Prepared by Double Emulsion Method. Chemical Research in Chinese Universities, 2010. 26(1): p. 136-141.
26. Yang, Y.Y., et al., Effect of preparation conditions on morphology and release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion method. Chemical Engineering Science, 2000. 55(12): p. 2223-2236.
27. Van Grieken, R.E. Markowicz, A.AHandbook of x-ray spectrometry: Methods and techniques, 1993.
28. John J. Bozzola, Lonnie D. Russell, Electron Microscopy, 2nd edition.
29. D. A. Skoog and J. J. Leary, Principles of Instrumental Analysis, 4th edition.
30. 王應瓊, 儀器分析, 中央圖書出版社
31. Stephens, D.J. and V.J. Allan, Light microscopy techniques for live cell Imaging. Science, 2003. 300(5616): p. 82-