pH-responsive polymer vesicles assembled from lipid-contaning poly(γ-glutamic acid ) and their applications in drug delivery

• Main Author: 王晢旭
• Other Authors: 邱信程
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/88569342183263034880

碩士 === 國立清華大學 === 生醫工程與環境科學系 === 99 === 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.