Antibacterial efficacy and pharmacokinetics of a poly(mPEG-b-PCEA)–trimethoprim conjugate

Abstract

Research into antimicrobials is crucial for the sustainable development of the livestock industry. Trimethoprim (TMP) is one of the most widely used antimicrobial agents in the world. However, its efficacy is often limited by poor water solubility and dose-limiting properties. In this work, amphiphilic block polymer carriers are prepared using the oxygen-induced reversible addition–fragmentation chain transfer polymerization reaction. TMP is linked to carriers in different ratios to form poly(mPEG-b-PCEA)–TPM conjugates. The conjugates are characterized using various methods including ¹H NMR, FT-IR, XRD and SEM. The results of in vitro antimicrobial experiments show that poly(mPEG-b-PCEA)–TMP with different ratios has more prominent antimicrobial effects than the same dosage of pure TMP. poly(mPEG-b-PCEA)–TMP₈₀ shows the most significant results, inhibiting E. coli by 87.19% and S. aureus by 97.02%, with a hemolysis rate of <5% and good biocompatibility. In vivo pharmacokinetics show an increase in C_max from 4.81 μg mL⁻¹ to 6.57 μg mL⁻¹ and AUC_0–48 from 78.55 h μg mL⁻¹ to 89.11 h μg mL⁻¹ for poly(mPEG-b-PCEA)–TMP₈₀ compared to commercially available TMP tablets. This strategy can effectively improve the antibacterial activity and pharmacokinetics and increase the bioavailability of TMP.