Polymeric micelles containing resveratrol: development, characterization, cytotoxicity on tumor cells and antimicrobial activity

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

白藜芦醇（resveratrol）是一种主要存在于葡萄中的化合物，其抗菌与抗肿瘤活性已得到证实。然而，其较低的生物利用度是制约其治疗应用的关键因素。聚合物胶束（polymeric micelles）可作为解决该问题的可行方案，因其能够包封疏水性物质。本研究开发并表征了负载白藜芦醇的胶束制剂，并对其细胞毒性与抗菌活性进行了评估。该系列制剂采用冷分散法制备，使用了不同浓度的F127（5%或10% w/w）与白藜芦醇（500或5000 µM）。随后通过粒径、多分散性指数、pH值、包封率及体外释放特性对制剂进行了表征。细胞毒性评估采用膀胱癌细胞系，抗菌活性则分别针对大肠杆菌（E. coli）、金黄色葡萄球菌（S. aureus）与白色念珠菌（C. albicans）开展。其中一种制剂（10% w/w F127与5000 µM白藜芦醇）为单分散溶液且包封率较高，因此被选用于后续的细胞毒性与抗菌活性测试。MS-10+RES-3可完整保留白藜芦醇的抗菌与细胞毒性活性。本研究为首次评估负载白藜芦醇的胶束对膀胱癌细胞的抗菌潜力与细胞毒性的研究，结果表明，胶束纳米结构可有效维持白藜芦醇的生物活性。