Kamenova Katya, Radeva Lyubomira, Konstantinov Spiro, Petrov Petar D, Yoncheva Krassimira
Institute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Str. 103A, 1113 Sofia, Bulgaria.
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
Polymers (Basel). 2023 Sep 14;15(18):3769. doi: 10.3390/polym15183769.
In this study, we report the development of a micellar system based on a poly(methacrylic acid)--poly(ε-caprolactone)--poly(methacrylic acid) triblock copolymer (PMAA-b-PCL-b-PMAA) for the oral delivery of resveratrol. The micellar nanocarriers were designed to comprise a PCL core for solubilizing the poorly water-soluble drug and a hydrated PMAA corona with bioadhesive properties for providing better contact with the gastrointestinal mucosa. The micelles were first formed in an aqueous media via the solvent evaporation method and then loaded with resveratrol (72% encapsulation efficiency). Studies by transmission electron microscopy (TEM) and dynamic and electrophoretic light scattering (DLS and PALS) revealed a spherical shape, nanoscopic size (100 nm) and a negative surface charge (-30 mV) of the nanocarriers. Loading of the drug slightly decreased the hydrodynamic diameter (Dh) and increased the ƺ-potential of micelles. In vitro dissolution tests showed that 80% and 100% of resveratrol were released in 24 h in buffers with pH 1.2 and 6.8, respectively, whereas for the same time, not more than 10% of pure resveratrol was dissolved. A heat-induced albumin denaturation assay demonstrated the advantage of the aqueous micellar formulation of resveratrol, which possessed anti-inflammatory potential as high as that of the pure drug. Further, the micellar resveratrol (5 µM) exerted a strong protective effect and maintained viability of mucosa epithelial HT-29 cells in a co-cultural model, representing the production of inflammatory cytokines. For comparison, the pure resveratrol at the same concentration did not protect the damaged HT-29 cells at all. Thus, the present study revealed that the PMAA--PCL--PMAA copolymeric micelles might be considered appropriate nanocarriers for the oral delivery of resveratrol.
在本研究中，我们报道了一种基于聚（甲基丙烯酸）-聚（ε-己内酯）-聚（甲基丙烯酸）三嵌段共聚物（PMAA-b-PCL-b-PMAA）的胶束系统用于白藜芦醇口服给药的研发。胶束纳米载体设计为由用于溶解难溶性药物的聚己内酯核心和具有生物黏附特性的水合聚甲基丙烯酸冠层组成，以实现与胃肠道黏膜的更好接触。胶束首先通过溶剂蒸发法在水性介质中形成，然后负载白藜芦醇（包封率为72%）。透射电子显微镜（TEM）以及动态和电泳光散射（DLS和PALS）研究表明，纳米载体呈球形，尺寸为纳米级（100 nm），表面带负电荷（-30 mV）。药物负载略微降低了胶束的流体动力学直径（Dh）并增加了其ζ电位。体外溶出试验表明，表示炎症细胞因子产生的白藜芦醇在pH 1.2和6.8的缓冲液中分别在24小时内释放了80%和100%，而在相同时间内，纯白藜芦醇的溶解量不超过10%。热诱导白蛋白变性试验证明了白藜芦醇水性胶束制剂的优势，其抗炎潜力与纯药物相当。此外，胶束白藜芦醇（5 μM）在共培养模型中对黏膜上皮HT-29细胞发挥了强大的保护作用并维持了其活力。相比之下，相同浓度的纯白藜芦醇根本没有保护受损的HT-29细胞。因此，本研究表明，PMAA-PCL-PMAA共聚物胶束可能被认为是白藜芦醇口服给药的合适纳米载体。
