Tang Jihui, Yao Jing, Shi Jingbo, Xiao Qingpin, Zhou Jianping, Chen Feihu
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
Pharmazie. 2012 Sep;67(9):756-64.
A novel block copolymer containing two polymeric components, poly(L-aspartic acid)-b-poly (L-phenylalanine) (PAA-PPA), was synthesized and its potential for the preparation of copolymer micelles with a poorly water-soluble drug was investigated in this study. The chemical structure and physical properties of PAA-PPA were characterized by FTIR, 1H NMR and TG. The degree of polymerization of PAA-PPA was calculated by analyzing the relative area of N-CH signal and C-CH3 of 1H NMR spectra. The critical micelle concentration (CMC) of the PAA-PPA achieved a minimum of 11.1 mg/L. Studies on the drug-free PAA-PPA solutions showed PAA-PPA aggregation into micellar type in the sub-150 nm size range. Furthermore, the size of the PAA-PPA micelles was found to be pH-independent between the pH range of 4.0 and 8.0, which could be favorable to avoid the limitation of the size change at the specified pH value seeking drug stability. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was studied as a poorly water-soluble model drug. The drug-loading and entrapment efficiency of the ATPR-loaded PAA-PPA micelles were 30.9 wt% and 87.9 %, respectively. The high drug-loading and entrapment efficiency were due to the synergistic effect of the micellar encapsulation and the binding interaction between drug and PAA-PPA. The ATPR-loaded PAA-PPA micelles showed a narrow size distribution, low zeta potential, high drug-loading capacity and good stable. The PAA-PPA was safer than Tween-80 and Cremophor EL (CrmEL) as an injectable pharmaceutical adjuvant for ATPR as indicated by the hemolysis and cytotoxicity studies. The novel amphiphilic amino acid copolymer can be considered as a prospective injectable delivery system for ATPR in terms of the pH-independent, greater drug-loading capacity and safety.
合成了一种含有两种聚合物组分的新型嵌段共聚物聚（L-天冬氨酸）-b-聚（L-苯丙氨酸）（PAA-PPA），并在本研究中考察了其用于制备载水溶性差的药物的共聚物胶束的潜力。通过傅里叶变换红外光谱（FTIR）、核磁共振氢谱（1H NMR）和热重分析（TG）对PAA-PPA的化学结构和物理性质进行了表征。通过分析1H NMR谱中N-CH信号和C-CH3的相对面积计算PAA-PPA的聚合度。PAA-PPA的临界胶束浓度（CMC）最低达到11.1 mg/L。对不含药物的PAA-PPA溶液的研究表明，PAA-PPA在尺寸小于150 nm的范围内聚集成胶束类型。此外，发现PAA-PPA胶束的尺寸在4.0至8.0的pH范围内与pH无关，这有利于避免在寻求药物稳定性的特定pH值下尺寸变化的限制。以4-氨基-2-三氟甲基苯基维甲酸酯（ATPR）作为水溶性差的模型药物进行了研究。载ATPR的PAA-PPA胶束的载药量和包封率分别为30.9 wt%和87.9%。高载药量和包封率归因于胶束包封的协同作用以及药物与PAA-PPA之间的结合相互作用。载ATPR的PAA-PPA胶束表现出窄的尺寸分布、低的zeta电位、高的载药能力和良好的稳定性。溶血和细胞毒性研究表明，作为ATPR的可注射药物辅料，PAA-PPA比吐温80和聚氧乙烯蓖麻油（CrmEL）更安全。就pH无关性、更高的载药能力和安全性而言，这种新型两亲性氨基酸共聚物可被视为ATPR的一种有前景的可注射给药系统。
