Triclosan-loaded pH-responsive copolymer to target bacteria and to have long bacteriostatic efficacy

Abstract

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.