This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC...This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and ~1H-NMR. The buffering capacity of polyethylene glycol-distearoyl phosphatidylethanolamine(PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel(DOC) liposomes(TPOS-DOC-L) had a slower drugrelease rate at pH 7.4 similar to PEGylated-DOC liposomes(PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes(TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4( P < 0.01). Conversely, for PEGylated C6 liposomes(PEG-C6-L) and conventional C6 liposomes(C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes(DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-Lsignificantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.展开更多
目的:研究维生素E琥珀酸聚乙二醇酯(Vit E TPGS)作为一种新型乳化剂在聚酸酐紫杉醇微球中的应用,以提高微球质量。方法:以熔解浓缩聚合法制备聚[1,3-双(对羧基苯氧基)丙烷-癸二酸],利用Vit E TPGS和聚乙烯醇(PVA)分别作乳化剂,通过单乳...目的:研究维生素E琥珀酸聚乙二醇酯(Vit E TPGS)作为一种新型乳化剂在聚酸酐紫杉醇微球中的应用,以提高微球质量。方法:以熔解浓缩聚合法制备聚[1,3-双(对羧基苯氧基)丙烷-癸二酸],利用Vit E TPGS和聚乙烯醇(PVA)分别作乳化剂,通过单乳化方法制备紫杉醇微球。结果:Vit E TPGS作为微球乳化剂的用量只有0.1%,低于传统乳化剂PVA的10%,载药量和包封产率提高到8.51%,89.1%,在体外释药实验中,无明显突释现象,累积释药率达到85%。结论:相比于传统的乳化剂PVA,无论是在微球的制备还是在药物的包封产率上,Vit E TPGS都是一种更加有效安全的乳化剂。展开更多
研究了以4-二甲氨基吡啶为催化剂,由α-生育酚和琥珀酸酐合成α-生育酚琥珀酸酯(α-TOS)的酯化反应工艺和反应动力学。该合成反应最佳条件为:α-生育酚与琥珀酸酐配比为1∶3;催化剂用量1.5%;反应温度50℃;反应时间4 h,产率达84.5%,样品...研究了以4-二甲氨基吡啶为催化剂,由α-生育酚和琥珀酸酐合成α-生育酚琥珀酸酯(α-TOS)的酯化反应工艺和反应动力学。该合成反应最佳条件为:α-生育酚与琥珀酸酐配比为1∶3;催化剂用量1.5%;反应温度50℃;反应时间4 h,产率达84.5%,样品的纯度大于96%。通过对反应规律的研究,结果表明,在本实验条件下该合成反应表现为二级不可逆反应,表观活化能Ea=83.4 k J。展开更多
基金supported by National Natural Science Foundation of China (81102394)Natural Science Foundation of Liaoning Province (20170540575)
文摘This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and ~1H-NMR. The buffering capacity of polyethylene glycol-distearoyl phosphatidylethanolamine(PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel(DOC) liposomes(TPOS-DOC-L) had a slower drugrelease rate at pH 7.4 similar to PEGylated-DOC liposomes(PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes(TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4( P < 0.01). Conversely, for PEGylated C6 liposomes(PEG-C6-L) and conventional C6 liposomes(C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes(DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-Lsignificantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.
文摘目的:研究维生素E琥珀酸聚乙二醇酯(Vit E TPGS)作为一种新型乳化剂在聚酸酐紫杉醇微球中的应用,以提高微球质量。方法:以熔解浓缩聚合法制备聚[1,3-双(对羧基苯氧基)丙烷-癸二酸],利用Vit E TPGS和聚乙烯醇(PVA)分别作乳化剂,通过单乳化方法制备紫杉醇微球。结果:Vit E TPGS作为微球乳化剂的用量只有0.1%,低于传统乳化剂PVA的10%,载药量和包封产率提高到8.51%,89.1%,在体外释药实验中,无明显突释现象,累积释药率达到85%。结论:相比于传统的乳化剂PVA,无论是在微球的制备还是在药物的包封产率上,Vit E TPGS都是一种更加有效安全的乳化剂。
文摘研究了以4-二甲氨基吡啶为催化剂,由α-生育酚和琥珀酸酐合成α-生育酚琥珀酸酯(α-TOS)的酯化反应工艺和反应动力学。该合成反应最佳条件为:α-生育酚与琥珀酸酐配比为1∶3;催化剂用量1.5%;反应温度50℃;反应时间4 h,产率达84.5%,样品的纯度大于96%。通过对反应规律的研究,结果表明,在本实验条件下该合成反应表现为二级不可逆反应,表观活化能Ea=83.4 k J。
