Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petrópolis, 59072-570, Natal, RN, Brazil.
Department of Clinical Analysis, Federal University of Rio Grande do Norte, UFRN, Av. Gal. Gustavo Cordeiro de Farias s/n, Petropolis, 59012-570, Natal, RN, Brazil.
J Mater Sci Mater Med. 2019 Jan 8;30(1):12. doi: 10.1007/s10856-018-6214-6.
Drug delivery systems can overcome cancer drug resistance, improving the efficacy of chemotherapy agents. Poly (lactic acid) (PLA) microparticles are an interesting alternative because their hydrophobic surface and small particle size could facilitate interactions with cells. In this study, two poloxamers (PLX 407 and 188) were applied to modulate the structural features, the drug release behavior and the cell viability from spray-dried microparticles. Five formulations with different PLA: PLX blend ratio (100:0, 75:25, 50:50, 25:50, and 0:100) were well-characterized by SEM, particle size analysis, FTIR spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis (XRD). The spray-dried microparticles showed higher drug loading, spherical-shape, and smaller particle size. The type of poloxamer and blend ratio affected their structural and functional properties such as morphology, crystallinity, blend miscibility, drug release rate, and cell viability. The methotrexate (MTX), a model drug, was loaded in amorphous spray-dried microparticles. Moreover, the drug release studies demonstrated that PLX induced a leaching-effect of MTX from PLA: PLX blends, suggesting the formation of MTX/PLX micelles in aqueous medium. This finding was better established by cell viability assays. Therefore, biocompatible PLA: PLX blends showed promising in vitro results, and further in vivo studies will be performed to evaluate the performance of this chemotherapeutic agent.
药物传递系统可以克服癌症药物耐药性，提高化疗药物的疗效。聚乳酸（PLA）微球是一种很有前途的替代品，因为其疏水性表面和较小的粒径有助于与细胞相互作用。在这项研究中，两种泊洛沙姆（PLX407 和 188）被应用于调节喷雾干燥微球的结构特征、药物释放行为和细胞活力。通过 SEM、粒径分析、傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）和 X 射线衍射分析（XRD）对具有不同 PLA：PLX 混合比（100:0、75:25、50:50、25:50 和 0:100）的五种制剂进行了很好的表征。喷雾干燥微球具有较高的载药量、球形和较小的粒径。泊洛沙姆的类型和混合比对其结构和功能性质有影响，如形态、结晶度、混合相容性、药物释放率和细胞活力。作为模型药物的甲氨蝶呤（MTX）被负载在无定形喷雾干燥微球中。此外，药物释放研究表明，PLX 诱导 MTX 从 PLA：PLX 混合物中溶出，表明在水介质中形成了 MTX/PLX 胶束。细胞活力测定进一步证实了这一发现。因此，具有生物相容性的 PLA：PLX 混合物在体外表现出有希望的结果，将进一步进行体内研究来评估这种化疗药物的性能。
