Dai Shulin, Feng Yucheng, Li Shuyi, Chen Yuxiao, Liu Meiqing, Zhang Chao, Zhang Wei, Yin Yihua
Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instruments, School of Engineering, Sun Yat-Sen University, Guangzhou, 510006, China.
School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, 430070, China.
Anticancer Agents Med Chem. 2018;18(2):302-311. doi: 10.2174/1871520617666170911170104.
Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release.
AIMS/METHODS: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles.
Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.
作为药物载体的胶束，由于促进两亲性嵌段共聚物自组装的弱物理相互作用而具有固有的不稳定性。作为强物理相互作用之一，等量摩尔的对映体聚丙交酯，即聚（L-丙交酯）（PLLA）和聚（D-丙交酯）（PDLA）之间的立体络合，可用于获得具有更高稳定性和载药量以及随之而来的缓释效果的胶束。
目的/方法：在本文中，立体络合胶束（γ-PGA-g-PLA胶束）由聚（γ-谷氨酸）-接枝-PLLA（γ-PGA-g-PLA）和聚（γ-谷氨酸）-接枝-PDLA（γ-PGA-g-PLA）之间的立体络合制备而成。这些立体络合胶束的临界胶束浓度低于相应的对映体胶束。
此外，它们在体外表现出更高的载药量和载药效率，以及更持久的药物释放曲线。体内成像证实，包封DiR的立体络合γ-PGA-g-PLA胶束能够将抗癌药物递送至肿瘤，且具有增强的组织穿透力。总体而言，与游离药物相比，γ-PGA-g-PLA胶束表现出更强的抗癌效果，立体络合可能是制备具有显著增强疗效的抗癌药物载体的一种有前景的策略。
