Influence of molecular weight on kinetics release of metronidazole from proline-based polymers prepared by RAFT polymerization

Abstract

In the current study, the influence of polymer molecular weight on the release of metronidazole (MTZ) as a drug model from synthesized proline-based polymers was studied. Using reversible-addition fragmentation chain transfer (RAFT) polymerization, amino acid-based polymers based on N-acryloyl-L-proline (A-L-Pro-OH) with various molecular weights were prepared with relatively high conversions (55–98%, as measured by ¹H NMR spectroscopy). The polymerization process was done at different ratios of [monomer]₀/[CTA]₀/[AIBN]₀. Proline-based polymers with pre-determined molecular weights (M_n = 6000–22 600 in methylated forms) and low polydispersities (M_w/M_n = 1.30–1.37) were utilized for the immobilization of metronidazole. The kinetics release studies of the polymer-MTZ adducts were done at various pH values: 2.0, 7.4, and 8.5 phosphate buffer solutions. The obtained results proved that the hydrolytic behaviors of polymeric prodrugs robustly relied on the molecular weight of the polymer and the pH of the release media. The kinetics of the release process were described using Higuchi and Korsmeyer's models to explain the drug release mechanism.