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Polymer 2009: Synthesis and self-assembly of amphiphilic poly(acrylic acid-b-DL-lactide) to form micelles for pH-responsive drug delivery
來源:黃世文教授個人網站 發布日期:2010-01-07
作者:Xue YN, Huang ZZ, Zhang JT, Liu M, Zhang M, Huang SW*, ZHuo RX*
關鍵字:Drug delivery
論文來源:期刊
具體來源:Polymer, 2009, 50(15), 3706-3713
發表時間:2009年

An amphiphilic diblock copolymer of poly(acrylic acid-b-DL-lactide) (PAAc-b-PDLLA) was synthesized by ring-opening polymerization Of X-lactide initiated by hydroxyl-terminated polyacrylic acid (PAAc-OH). The critical micelle concentration (CMC) of PAAc-b-PDLLA in aqueous solution, determined by fluorescence spectroscopy using pyrene as a probe, was found about 80 mg L-1. A solution of PAAc-b-PDLLA in tetrahydrofuran (THF) was dialyzed against pure water to form pH-responsive micelles. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited regular spherical morphology and the diameters of particles were in the range from 40 to 90 nm. The micelles were stable at a pH above 3 or at an ionic strength below 1.0, however, they aggregated and precipitated in the solutions when further decreasing pH or increasing ionic strength. Prednisone acetate, as a model hydrophobic drug, was loaded into the polymeric micelles. In vitro release of prednisone acetate from polymeric micelles showed that the release kinetics was strongly pH-dependent. Hydrophobic drug displayed "burst" release at pH 7.4, while only a small part of loaded drug released at pH 1.4. This provides a new choice to design delivery system for the gastrointestinal tract (GI tract), where the pH environment is strongly acidic in stomach and basic in intestine. The cytotoxicity measurement by MTT assay indicated that PAAc-b-PDLLA was low toxic in HeLa cells with an IC50 value of 2.8 mg mL(-1), which suggests that PAAc-b-PDLLA could be used as a safe candidate for pH-responsive drug delivery.

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