Laboratory for Polymer Analysis, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, Kerala, India.
J Pharm Sci. 2011 Feb;100(2):504-11. doi: 10.1002/jps.22278. Epub 2010 Sep 16.
Curcumin has been studied as a potential drug for many diseases including cancer. One of the serious limitations projected on curcumin is its poor water solubility and the substantially low bioavailability. With a view to enhance the aqueous solubility of curcumin, we synthesized polyvinylpyrrolidone-curcumin conjugates. Polyvinylpyrrolidone was used for the conjugation considering its long history of safe usage as a biomaterial for various medical applications. The drug conjugates self-assembled in aqueous solution to form nanosized micellar aggregates. The formation of micellae stabilized curcumin against hydrolytic degradation. Another interesting feature of the conjugate was its cationic nature. The net zeta potential in the pH range from 3 to 7.4 was +25 to +20 mV, reflecting the potential stability of the conjugate micellae at physiological pH. We quantified cytotoxic potential of the conjugate by the MTT assay, using L929 fibroblast cells. The results showed that the conjugate had higher cytotoxicity than that of the free curcumin. It is expected that the relative enhanced cytotoxicities are the result of enhanced aqueous solubility and polymer-mediated drug internalization. The conjugate has the potential to circumvent limitations of curcumin and thereby to extrapolate further its applications as an effective anticancer drug.
姜黄素已被研究作为治疗多种疾病（包括癌症）的潜在药物。姜黄素的一个严重限制是其较差的水溶性和极低的生物利用度。为了提高姜黄素的水溶性，我们合成了聚乙烯吡咯烷酮-姜黄素缀合物。考虑到聚乙烯吡咯烷酮作为生物材料在各种医疗应用中的安全使用历史悠久，因此将其用于缀合。药物缀合物在水溶液中自组装形成纳米级胶束聚集体。胶束的形成稳定了姜黄素，防止其水解降解。该缀合物的另一个有趣特性是其阳离子性质。在 pH 值为 3 到 7.4 的范围内，净 ζ 电位为+25 到+20 mV，反映了在生理 pH 值下，该缀合物胶束的潜在稳定性。我们通过 MTT 测定法，使用 L929 成纤维细胞来定量测定该缀合物的细胞毒性潜力。结果表明，该缀合物比游离姜黄素具有更高的细胞毒性。预计相对增强的细胞毒性是由于增强的水溶性和聚合物介导的药物内化所致。该缀合物有可能克服姜黄素的局限性，从而进一步将其应用于作为有效的抗癌药物。
