Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, China.
AAPS PharmSciTech. 2021 Jan 6;22(1):38. doi: 10.1208/s12249-020-01885-9.
The objective of this study was to encapsulate the poorly water-soluble drug TM-2 into polymer micelles using mPEG-b-PLA to increase its aqueous solubility and improve its therapeutic effect for liver cancer. Furthermore, in order to achieve long-term storage, the micelle solution was successfully freeze-dried. This study theoretically clarified the possibility of enhancing the water solubility of TM-2 using mPEG-b-PLA micelles as well as the protective effects of mixed lyoprotectants. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were performed, which showed that the drug has a good affinity with the polymer (χ = 0.489) according to Flory-Huggins theory and that lyoprotectants reduced the crystallinity of PEG in mPEG-b-PLA and played a space-protective role in the lyophilization process. In vivo experiments showed that micellization could improve the drug bioavailability and give a high therapeutic effect with a tumor inhibition rate of 84.5% under the tolerated dose.
本研究旨在通过 mPEG-b-PLA 将疏水性差的药物 TM-2 包封在聚合物胶束中，以提高其水溶解度并改善其对肝癌的治疗效果。此外，为了实现长期储存，成功地对胶束溶液进行了冷冻干燥。本研究从理论上阐明了使用 mPEG-b-PLA 胶束来提高 TM-2 的水溶性以及混合保护剂的保护作用的可能性。差示扫描量热法（DSC）、X 射线衍射（XRD）和扫描电子显微镜（SEM）的结果表明，根据 Flory-Huggins 理论，药物与聚合物具有良好的亲和力（χ=0.489），并且保护剂降低了 mPEG-b-PLA 中 PEG 的结晶度，并在冷冻干燥过程中发挥空间保护作用。体内实验表明，胶束化可以提高药物的生物利用度，并在耐受剂量下以 84.5%的肿瘤抑制率产生高治疗效果。
