College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China.
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China.
Eur J Pharm Sci. 2020 May 30;148:105320. doi: 10.1016/j.ejps.2020.105320. Epub 2020 Mar 31.
It is important to reduce side effects and to explore novel usage for hydrophobic broad-spectrum antibacterial agent triclosan (TCS). In this study, a new amphiphilic copolymer with tertiary amine groups, monomethyl ether poly(ethylene glycol)-b-poly{α-[4-(diethylamino)methyl-1,2,3-triazol]-caprolactone-co-caprolactone} (mPEG-PDCL) was designed and synthesized, and its micelles were applied as carries of TCS to enhance antimicrobial and bacteriostatic action. mPEG-PDCL and its contrastive copolymer mPEG-PCL could form uniform spherical micelles with sizes 50-110 nm. The zeta potential of mPEG-PDCL micelles was positive and changed from 7.00 ± 0.67 mV at pH 7.5 to 24.67 ± 1.23 mV at pH 5.5. Both TCS-loaded micelles displayed quite high drug loading content (approx. 15%) and drug loading efficiency (more than 85%). In comparison with pH 7.4, TCS released faster in acidic environment which was induced by bacteria metabolism. MIC values of both TCS-loaded micelles against S. aureus and E. coli were as low as free TCS. TCS-loaded micelles showed much better antibacterial activity than free TCS, especially, mPEG-PDCL/TCS micelles displayed long bacteriostatic efficacy in 60 h against S. aureus and in 54 h against E. coli. mPEG-PDCL micelles preferred targeting to both S. aureus and E. coli due to positive zeta potential. In in vivo experiment, the purulence of the infected wound almost disappeared for SD rats treated with mPEG-PDCL/TCS micelles. Therefore, mPEG-PDCL micelles may be used as good carriers for antimicrobial agents, and the TCS-loaded micelles possess long antimicrobial/bacteriostatic efficacy.
降低副作用并探索新型疏水性广谱抗菌剂三氯生（TCS）的新用途非常重要。在这项研究中，设计并合成了一种带有叔胺基团的新型两亲性共聚物，单甲醚聚乙二醇-b-聚{α-[4-（二乙氨基）甲基-1,2,3-三唑]-己内酯-co-己内酯}（mPEG-PDCL），并将其胶束用作 TCS 的载体，以增强抗菌和抑菌作用。mPEG-PDCL 和其对比共聚物 mPEG-PCL 可以形成粒径为 50-110nm 的均匀球形胶束。mPEG-PDCL 胶束的 ζ 电位为正，从 pH7.5 时的 7.00±0.67mV 变化到 pH5.5 时的 24.67±1.23mV。载 TCS 的胶束均显示出相当高的载药量（约 15%）和载药效率（超过 85%）。与 pH7.4 相比，TCS 在由细菌代谢诱导的酸性环境中释放更快。载 TCS 的胶束对金黄色葡萄球菌和大肠杆菌的 MIC 值与游离 TCS 相当。载 TCS 的胶束比游离 TCS 具有更好的抗菌活性，特别是 mPEG-PDCL/TCS 胶束对金黄色葡萄球菌的抑菌效果长达 60h，对大肠杆菌的抑菌效果长达 54h。由于正 ζ 电位，mPEG-PDCL 胶束更倾向于靶向金黄色葡萄球菌和大肠杆菌。在体内实验中，用 mPEG-PDCL/TCS 胶束处理的 SD 大鼠的感染伤口的脓液几乎消失。因此，mPEG-PDCL 胶束可用作抗菌剂的良好载体，载 TCS 的胶束具有长效的抗菌/抑菌效果。
