Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal, India.
Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal, India.
Int J Biol Macromol. 2024 Apr;263(Pt 2):130372. doi: 10.1016/j.ijbiomac.2024.130372. Epub 2024 Feb 21.
The present study reports the synthesis of micellar conjugates, wherein curcumin (Cur), a bioactive compound with poor bioavailability, was covalently bonded to a bacterial exopolysaccharide (EPS). These conjugates were synthesized by utilizing succinic acid that linked Cur to the pyranosyl moiety of the EPS. The Cur-EPS conjugates appeared as spherical micelles in aqueous solution and were found to have an average hydrodynamic diameter of 254 ± 2.7 nm. The micellar conjugates showed superior stability than Cur as evident from their negative surface charge (-27 ± 1.8 mV) and low polydispersity index (PDI) (0.33 ± 0.04). The in vitro studies on release kinetics helped elucidate the pH-responsive characteristics of the Cur-EPS conjugate, as 87.50 ± 1.45 % of Cur was released at an acidic pH of 5.6, in contrast to 30.15 ± 2.61 % at systemic pH of 7.4 at 150 h. The conjugates were hemocompatible and exhibited cytotoxic effect against the osteosarcoma cell line (MG-63) after 48 h treatment. They also demonstrated superior antibacterial, antibiofilm, and antioxidant activities in comparison to free Cur. Therefore, the Cur-EPS conjugates have potential pharmaceutical applications as therapeutic biomaterial that can be applied as a drug delivery system.
本研究报告了胶束缀合物的合成,其中姜黄素(Cur)是一种生物利用度较差的生物活性化合物,它通过琥珀酸共价键合到细菌胞外多糖(EPS)上。这些缀合物是通过利用将 Cur 连接到 EPS 的吡喃糖部分的琥珀酸合成的。Cur-EPS 缀合物在水溶液中呈现球形胶束,平均水动力直径为 254 ± 2.7nm。与 Cur 相比,胶束缀合物表现出更好的稳定性,其表面带负电荷(-27 ± 1.8mV)和低多分散指数(PDI)(0.33 ± 0.04)。释放动力学的体外研究有助于阐明 Cur-EPS 缀合物的 pH 响应特性,因为在酸性 pH 值 5.6 下,87.50 ± 1.45%的 Cur 被释放,而在系统 pH 值 7.4 下,150 小时后仅释放 30.15 ± 2.61%。缀合物具有血液相容性,并在 48 小时治疗后对骨肉瘤细胞系(MG-63)表现出细胞毒性作用。与游离 Cur 相比,它们还表现出优异的抗菌、抗生物膜和抗氧化活性。因此,Cur-EPS 缀合物具有作为治疗生物材料的潜在药物应用,可作为药物传递系统。