Zhang Zongrui, Wang Xinyu, Li Binbin, Hou Yuanjing, Cai Zhengwei, Yang Jing, Li Yi
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology Wuhan 430070 China
Biomedical Materials and Engineering Research Center of Hubei Province Wuhan 430070 China.
RSC Adv. 2018 Jan 16;8(6):3274-3285. doi: 10.1039/c7ra12683b. eCollection 2018 Jan 12.
The aim of this study was to develop a novel morphological paclitaxel (PTX) loaded poly(lactide--glycolide) (PLGA) microspheres (MS) delivery system to enhance drug delivery and antitumor efficiency as well as reduce drug administration frequency. Therefore, different morphological types of PTX-PLGA-MS were prepared using a modified solvent evaporation technique. Morphology analysis confirmed the successful preparation of the smooth PTX-PLGA-MS with internal sporadic porosity, and the novel rough PTX-PLGA-MS with microporous surface and porous internal structures. The PTX drugs were distributed in the readily bioavailable state (amorphous) in PTX-loaded MS, which allowed fast drug release from MS following intratumoral administration. The drug entrapment and release behaviors indicated that the rough MS could provide enough hydrophobic space for PTX-loading and deep surface folds for fast matrices degradation, thus achieving a higher drug-loading efficiency (17.8%) and a rapid sustained drug release effect. Furthermore, the rough MS showed strengthened anti-hepatoma efficiency than that of free PTX and smooth MS. The studies indicated remarkable antitumor activity of rough MS (tumor inhibition rate = 58.33%) for at least 13 days after a single injection, which was because the rapid sustained-release drugs could induce the pro-apoptosis gene and protein expressions, cause extensive tumor cell apoptosis, and reduce the toxicity to normal tissues. In conclusion, the rough PTX-PLGA-MS drug delivery system with outstanding tumor growth inhibition effect could serve as a promising treatment for liver tumor.
本研究的目的是开发一种新型的负载形态学紫杉醇（PTX）的聚（丙交酯-乙交酯）（PLGA）微球（MS）给药系统，以提高药物递送和抗肿瘤效率，并减少给药频率。因此，采用改良的溶剂蒸发技术制备了不同形态类型的PTX-PLGA-MS。形态学分析证实成功制备了具有内部散在孔隙的光滑PTX-PLGA-MS，以及具有微孔表面和多孔内部结构的新型粗糙PTX-PLGA-MS。PTX药物以易于生物利用的状态（无定形）分布在负载PTX的MS中，这使得在瘤内给药后药物能从MS中快速释放。药物包封和释放行为表明，粗糙的MS可以为PTX负载提供足够的疏水空间，并为快速的基质降解提供深层表面褶皱，从而实现更高的载药效率（17.8%）和快速的持续释药效果。此外，粗糙的MS显示出比游离PTX和平滑MS更强的抗肝癌效率。研究表明，单次注射后，粗糙的MS具有显著的抗肿瘤活性（肿瘤抑制率=58.33%），至少持续13天，这是因为快速持续释放的药物可以诱导促凋亡基因和蛋白表达，导致广泛的肿瘤细胞凋亡，并降低对正常组织的毒性。总之，具有出色肿瘤生长抑制效果的粗糙PTX-PLGA-MS给药系统有望成为肝癌的一种治疗方法。
