Bagheri Massoumeh, Bigdeli Elham, Pourmoazzen Zhaleh
Chemistry Department, Science Faculty, Azarbaijan Shahid Madani University, P.O. Box: 53714-161, 5375171379, Tabriz, Iran.
Prog Biomater. 2014 Apr 3;3(1):22. doi: 10.1007/s40204-014-0022-y.
Present research is a preliminary report on the novel pH-responsive micelles based on an amphiphilic brush copolymer P(PEGMA)-b-P(DMAEMA-co-CPLAMA) used as the promising drug carrier. The copolymer was synthesized using cholesteryl poly(L-lactic acid) methacrylate (CPLAMA), poly(ethylene glycol) monomethyl ether methacrylate (PEGMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) with appropriate hydrophobic/hydrophilic ratios via atom transfer radical polymerization. The copolymer compositions were determined by H NMR. The synthesized copolymer self-assembled into nano-scale micelles capable of encapsulating hydrophobic model drug naproxen in their hydrophobic cores in aqueous solutions. pH sensitivity and self-assembly behaviors of copolymer were studied by UV-vis transmittance, fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The results showed that the copolymer had high pH responsivity with a phase transition pH around pH 6.2. The critical micelle concentrations at pH 6.5 were found about 2.4 mg L. The stable and small micelles were obtained at pH 5.5-6.5. Upon increasing pH higher than 7, the single micelles further assembled into the micellar aggregates. TEM images of copolymer micelles showed that the micelles are spherical in shape with the mean diameter of 152 nm at pH 6.2. In vitro release study of naproxen-loaded micelles with about 44 % loading efficiency and 8 % loading capacity was performed using dialysis method in phosphate-buffered solution at 37 °C. Release study implied that the proposed brush copolymer could produce stable nano-carriers with controllable drug release at the target sites (pH 5.5-7).
本研究是关于一种新型pH响应性胶束的初步报告，该胶束基于两亲性刷状共聚物P(PEGMA)-b-P(DMAEMA-co-CPLAMA)，用作有前景的药物载体。通过原子转移自由基聚合反应，使用具有适当疏水/亲水比例的胆固醇基聚(L-乳酸)甲基丙烯酸酯(CPLAMA)、聚(乙二醇)单甲醚甲基丙烯酸酯(PEGMA)和甲基丙烯酸2-(二甲氨基)乙酯(DMAEMA)合成了该共聚物。通过核磁共振氢谱(H NMR)确定共聚物组成。合成的共聚物在水溶液中自组装成纳米级胶束，能够将疏水性模型药物萘普生包裹在其疏水核中。通过紫外可见透光率、荧光光谱、透射电子显微镜(TEM)和动态光散射研究了共聚物的pH敏感性和自组装行为。结果表明，该共聚物具有较高的pH响应性，相变pH约为6.2。发现在pH 6.5时的临界胶束浓度约为2.4 mg/L。在pH 5.5 - 6.5时获得了稳定且小的胶束。当pH升高到7以上时，单个胶束进一步组装成胶束聚集体。共聚物胶束的TEM图像显示，在pH 6.2时胶束呈球形，平均直径为152 nm。使用透析法在37°C的磷酸盐缓冲溶液中对载药量约为44%、载药率为8%的萘普生负载胶束进行了体外释放研究。释放研究表明，所提出的刷状共聚物可以产生稳定的纳米载体，在靶部位(pH 5.5 - 7)实现可控药物释放。
