Chen Hsuan-Ying, Lo Yu-Lun, Wu Pei-Ling, Lo Pei-Chi, Wang Li-Fang
Department of Medicinal & Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Department of Medicinal & Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Colloids Surf B Biointerfaces. 2017 Aug 1;156:243-253. doi: 10.1016/j.colsurfb.2017.05.034. Epub 2017 May 12.
Novel comb-shaped amphiphilic copolymers based on methoxy poly(ethylene glycol)-b-[poly(ε-caprolactone)-g-poly(methacrylic acid)] (MPCL-g-pMAA), were synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) for drug delivery systems. MPCL-g-pMAAs with various MAA repeating units self-assemble into a core-shell structure in an aqueous solution. Critical aggregation concentrations range within 5.6×10-7.0×10mg/mL in double deionized water and 8.9×10-7.0×10mg/mL in phosphate buffered saline of pH 7.4, decreasing with increase in pMAA length. The carboxylic groups of MPCL-g-pMAAs were utilized to coordinate cisplatin, forming polymer-metal complexes for chemotherapy. The average hydrodynamic diameters of particles are within 220-246nm, slightly dependent on pMAA length. However, the cisplatin-loaded MPCL-g-pMAAs particles have average hydrodynamic diameters of 263-412nm owing to increasing drug loading efficiency with increase in pMAA length. Nevertheless, the MPCL-g-pMAA with the least number of MAA repeating unit shows the fastest drug release rate as well as the highest cytotoxicity against CRL-5802 cells. The cellular uptake of MPCL-g-pMAA particles, involving mainly clathrin-mediated endocytosis, increases with incubation time. MPCL-g-pMAA particles are non-cytotoxic to CRL-5802 cells but the cisplatin-loaded MPCL-g-pMAA particles show profound cell-killing ability. The MPCL-g-pMAA is a potential carrier for drug delivery systems.
基于甲氧基聚（乙二醇）-b-[聚（ε-己内酯）-g-聚（甲基丙烯酸）]（MPCL-g-pMAA）合成了新型梳状两亲共聚物，通过开环聚合（ROP）和原子转移自由基聚合（ATRP）用于药物递送系统。具有不同MAA重复单元的MPCL-g-pMAA在水溶液中自组装成核壳结构。在双去离子水中临界聚集浓度范围为5.6×10 - 7.0×10mg/mL，在pH 7.4的磷酸盐缓冲盐水中为8.9×10 - 7.0×10mg/mL，随pMAA长度增加而降低。MPCL-g-pMAA的羧基用于配位顺铂，形成用于化疗的聚合物-金属配合物。颗粒的平均流体动力学直径在220 - 246nm范围内，对pMAA长度略有依赖性。然而，由于随着pMAA长度增加药物负载效率提高，负载顺铂的MPCL-g-pMAA颗粒的平均流体动力学直径为263 - 412nm。尽管如此，具有最少MAA重复单元数量的MPCL-g-pMAA显示出最快的药物释放速率以及对CRL-5802细胞的最高细胞毒性。MPCL-g-pMAA颗粒的细胞摄取主要涉及网格蛋白介导的内吞作用，随孵育时间增加。MPCL-g-pMAA颗粒对CRL-5802细胞无细胞毒性，但负载顺铂的MPCL-g-pMAA颗粒显示出强大的细胞杀伤能力。MPCL-g-pMAA是药物递送系统的潜在载体。
