在本實驗中，利用二硬酯酸甘油脂修飾聚麩胺酸得到一雙性高分子( Poly( γ-glutamic acid-co-distearin glutamate ), γ-PGA-DSGA )，其於水相中( pH 7.4 )自組裝製備出粒徑約為150 nm的高分子奈米微粒。藉由DLS、SLS和TEM證實此微粒型態為高分子液胞結構。進一步地，於穩定性的實驗中，可發現脂質含量較高的高分子液胞可於4 ℃環境下保存至最少28天，而含量較少的液胞於室溫中或是4℃環境下穩定性皆不佳。
為賦予高分子液胞強烈的酸鹼應答特性及有效提高液胞穩定性，Chitosan及γ-PGA ( 或γ-PGA-PEG )利用正負電吸引力依序沉積於高分子液胞表面上，其仍可維持液胞結構。此高分子液胞可以將抗癌藥物DOX包覆於內部水相空間約八成，並且於pH 7.4水相中不洩漏。隨著溶液pH值下降，因GA單元轉變為不解離態及chitosan鏈段的質子化程度增加，使得液胞表面的電荷由負轉正，並且導致DOX的累積釋放量增加，此項實驗結果於體外釋放實驗中可被證實，在低pH值( pH 7.4 )大約可釋放約80 %。另外，由細胞存活率實驗中發現高分子複合液胞無細胞毒性；而包覆DOX的高分子複合液胞可有效抑制HeLa cell生長。此一具有酸鹼應答特性的高分子複合液胞有相當大的潛力於藥物傳遞系統之應用。

In this study, we used the biodegradable amphiphilic copolymers of lipid-modified poly(γ-glutamic acid) (Poly(γ-glutamic acid-co-distearin glutamate), γ-PGA-DSGA) prepared by modifying 1,2-distearoyl-rac-glycerol (distearin) as hydrophobic segments, onto poly(γ-glutamic acid) as the hydrophilic segments. The γ-PGA-based nanoparticles are prepared by self-assembly of amphiphilic copolymers in aqueous phase solution (pH 7.4 buffer). Combining the results of dynamic light scattering (DLS)、static light scattering (SLS) and transmission electron microscope (TEM), we strongly confirmed that the structure of assemblies is presented in vesicle-like form. Further, in stablization experiment, the vesicles with higher DSGA contents can be preserved in acqueous phase solution at 4℃ at least for 28 days. However, the vesicles with lower lipid contents are unstable either at room temperature or at 4℃.
To endow the capacity in pH responsibility and effectively increase the stability of copolymer vesicle, chitosan and γ-PGA (or γ-PGA-PEG) were sequentially deposited on the surface of copolymer vesicle via electrostatic attraction. With the solution pH being decreased, the zeta potential of copolumer vesicle surface was turned to positive from negative because GA residues and chitosan segments were protonated. In vitro drug release experiment, the accumulated release of DOX increases as the solution pH was decreased. Moreover, the DOX-free vesicles are non-cytotoxicity examined by the cell survival experiment, but DOX-loaded vesicles can effectively kill HeLa cell. Nevertheless, DOX-loaded vesicles showed a low capacity in killing MCF-7 cells due to approximately 40% of P-glycoprotein（P-gp）in breast cancer cell (MCF-7) .As a result, these pH-responsive polymer vesicles have great potential in the applications of drug delivery systems.

[1] Bangham, A. D.; Standish, M. M.; Weissmann, G. J. Mol. Biol. 1965, 13,
253-9.
[2] New RRC, Liposomes: a practical approach 1990, Oxford Univ. Press.
[3] Piertrzak, W. P. ; Miller, I. F. Biomat. Art. Cells, Art. Org., 1981, 17, 563-581
[4] B. P. Gaber, P. Yager, J. P. Shriedan and E. L. Chang, “, FEBS Lett. 1983, 153,
285-288.
[5] S. Kim G, M, Martin, , Biochem. Biophys. Acta. 1981, 646, 1-9
[6] Ahmed, F.; Discher, D. E. J. Control Release 2004, 96, 37-53.
[7] Zhang, L.; Eisenberg, A. Science 1995, 268, 1728-31.
[8] Holder, S. J.; Hiorns, R. C.; Sommerdijk, N. A. J. M.; Williams, T. J.; Jones, R.
G.; Nolte, R. J. M. Chem. Commum. 1998, 1445-6.
[9] Battaglia, G.; Ryan, A. J. J Phys Chem B 2006, 110, 10272-9.
[10] Stoenescu, R.; Meier, W. Chem Commun 2002, 3016-7.
[11] Uzun, O.; Xu, H.; Jeoung, E.; Thibault, R. J.; Rotello, V. M. Chemistry 2005,
11, 6916-20.
[12] Li, Y.; Lokitz, B. S.; McCormick, C. L. Angew. Chem. Int. Ed. Engl. 2006, 45,
5792-5.
[13] Choi, H. J.; Montemagno, C. D. Nano Lett. 2005, 5, 2538-42.
[14] Dufes, C.; Schatzlein, A. G.; Tetley, L.; Gray, A. I.; Watson, D. G.; Olivier, J.
C.; Couet, W.; Uchegbu, I. F. Pharm. Res. 2000, 17, 1250-8.
[15] Graff, A.; Sauer, M.; Van Gelder, P.; Meier, W. Proc. Natl. Acad. Sci. U. S. A.
2002, 99, 5064-8.
[16] Meier , W. Chem. Soc. Rev. 2000, 29, 295-303.
[17] Ringsdorf , H.; Schlarb, B.; Venzmer, J Angew. Chem. Int. Ed. 1988, 27,
113-158
[18] Discher, B. M.; Won, Y. Y.; Ege, D. S.; Lee, J. C.; Bates, F. S.; Discher, D. E.;
Hammer, D. A. Science 1999, 284, 1143-6.
[19] Owen, R. L. S. ; J. K. ; Breyer, E. D. Electrophoresis, 2005, 26, 735.
[20] Kim, K. T.; Cornelissen, J. J. L. M.; Nolte, R. J. M.; Hest, J. C. M.van. Adv.
Mater. 2009, 21, 2787–91.
[21] Chiu, H. C. ; Lin, Y.W. ; Huang, Y. F. ; Chuang, C. K. ; Chern, C. S. Angew.
Chem. Int. Ed. 2008, 47, 1875–1878.
[22] Discher ,D. E.;Eisenberg ,A. Science 2002, 297, 967-73
[23] Battaglia, G.; Ryan, A. J. J Phys Chem B 2006, 110, 10272-9.
[24] Owen, R. L.;Strasters, J. K.; Breyer, E. D. Electrophoresis 2005, 26, 735
[25] Du, J; Tang, Y; Lewis, A. L. ; Armes, S. P. J. Am. Chem. Soc.
2005,127,17982-83.
[26] Li, S.; Byrne, B.; Welsh, J.; Palmer, A. F. Biotechnol Prog. 2007, 23,
278-85.
[27] Wittemann, A.; Azzam, T.; Eisenberg, A. Langmuir 2007, 23,
2224-30.
[28] Lomas,H.;Canton, I.;MacNeil, S.;Du, J.;Armes , S. P.;Ryan, A. J.;Lewis,
A. L.;Battaglia,G. Adv. Mater. 2007, 19, 4238-43.
[29] Yokoyama, M.; Miyauchi, M.; Yamada, N.; Okano, T.; Sakurai, Y.; Kataoka,
K.; Inoue, S. Cancer Res. 1990, 50, 1693
[30] Lavasanifar, A.; Samuel, J.; Kwon, G. S. Adv. Drug Del. Rev. 2002, 54,169
[31] Allen, C.; Maysinger, D.; Eisenberg, A. Colloids Surf. B. 1999, 16, 3.
[32] D. Gan, and L. A. Lyon, J.Am. Chem. Soc., 2001, 123, 7511
[33] J. Wang, D. Gan, L. A. Lyon, M. A. El-Sayed, J. Am. Chem. Soc., 2001, 123,
11284
[34] D. Gan, and L. A. Lyon, J.Am. Macromolecules, 2002, 35, 9643
[35] Ivanovics, G., Bruckner, V. Z. Immunitatsforsch 1937, 90, 304.
[36] Rodriguez-Hernandez, J.; Lecommandoux, S. J. Am. Chem. Soc. 2005, 127,
2026-7.
[37] Sanson, C.; Schatz, C.; Le Meins, J. F.; Brulet, A.; Soum, A.; Lecommandoux,
S. Langmuir 2010, 26, 2751-60.
[38] Pusateri, A. E., S. J. McCarthy, K. W. Gregory, R. A. Harris, L. Cardenas, A.
T. McManus & C. W. Goodwin Jr. Trauma, 2003,54, 177–182.
[39] Zimm, B. H. J Chem Phys 1948, 16, 1093.
[40] Instruction Manual for Bi-200SM Goniometer ver.2.0 from Brookhaven
Instruments Corporation .
[41] Wang, C.;Ravi, P.;Tam, K. C.;Gan, L. H. J.Phys.Chem.B 2004,108,1621-7
[42] Goncü alves, C.; Martins, J. A.; Gama, F. M. Biomarcromolecules 2007, 8,
392-8
[43] Shen, H.; Eisenberg, A. Macromolecules 2000, 33, 2561-72
[44] Goncü alves, C.; Martins, J. A.; Gama, F. M. Biomarcromolecules 2007, 8,
392-8
[45] Shen, H.; Eisenberg ,A. Macromolecules 2000, 33, 2561-72
[46] Xu, Y.; Shi, L; Ma, R.; Zhang, W; An,Y.; Zhu, X. X. Polymer 2007, 48,1711-7
[47] Ma, Y.; Cao, T.; Webber, S. E. Marcromolecule 1998, 31, 1773-8
[48] Chiu, H. C. ; Lin, Y.W. ; Huang, Y. F. ; Chuang, C. K. ; Chern, C. S. Angew.
Chem. Int. Ed. 2008, 47, 1875–1878.
[49] Goncü alves, C.; Martins, J. A.; Gama, F. M. Biomarcromolecules 2007, 8,
392-8
[50] D. Gan, and L. A. Lyon, J.Am. Macromolecules, 2002, 35, 9643
[51] Ivanovics, G., Bruckner, V. Z. Immunitatsforsch 1937, 90, 304.
[52] Shen, H.; Eisenberg, A. Macromolecules 2000, 33, 2561-72
[53] Shen, H.; Eisenberg ,A. Macromolecules 2000, 33, 2561-72