Thermosensitive PNIPAm-based hydrogels for antibiotics release: Aging effect

Poly(N-isopropylacrylamide) (PNIPAm)-based polymers are undoubtedly a promising solution for controlled drug delivery. This study presents the potential of such hydrogels in terms of stability for drug delivery property. Aging under thermal oxidative aging at 120°C for 2 months is performed and its consequences on drug delivery are investigated. First, two active pharmaceutical ingredients (API) (metronidazole, MTZ and orbifloxacin, ORBI) and PNIPAm-based polymers are fully characterized. Linear poly(N-isopropylacrylamide) demonstrates an immediate release of antibiotic-type active pharmaceutical ingredients (MTZ and ORBI) at 25°C and 37°C with over 90% API release after 1-hour period. For more complex systems, such as cross-linked networks and copolymers, controlled release of ORBI at 25°C and 37°C is achieved over a 24-hour period and only 80% API release with an initial burst release phase. Results showed a slight increase in glass transition after aging at 120°C for 2 months with a decrease in the macromolecular mobility of the polymer. Structural modifications induced by aging lead to variations in the release behavior of APIs. Over time, the release slows down, and the overall efficacy of the system diminishes drastically. 19F is used as a probe to monitor ORBI release by quantitative NMR spectrometry, and diffusion coefficients are determined by Diffusion Ordered SpectroscopY (DOSY) to characterize API-Hydrogels interactions. This work extends our understanding of the stability of poly(N-isopropylacrylamide)-based polymers, enabling a rational approach of their use as pharmaceutical excipients.