Fuente: Journal of applied polymer Lugar: RESEARCH ARTICLE A dual pH- and temperature-responsive NIPAM-IA nanogel encapsulates a fusidic acid-HPβCD inclusion complex, overcoming poor drug solubility while enabling smart, stimuli-triggered release. The optimized formulation achieves 75.1% entrapment efficiency and pronounced pH-dependent swelling, sustaining 76.5% drug release over 48 h via anomalous transport. This synergistic platform offers a compelling strategy for targeted antibiotic delivery against skin infections and antimicrobial resistance.

ABSTRACT
The emergence of antimicrobial resistance (AMR) necessitates the development of innovative delivery systems capable of maintaining enhanced therapeutic concentrations at the infection site. This study presents an innovative dual temperature and pH-responsive nanogel system encapsulating poorly water-soluble antibiotic fusidic acid, complexed with hydroxypropyl-beta-cyclodextrin (HPβCD) to improve solubility and facilitate controlled topical drug release. The fusidic acid-HPβCD inclusion complex was synthesized to improve drug loading, and the resulting complex was encapsulated within nanogels (NGs). Fabricated via free radical polymerization, the optimized formulation (NIB-7) demonstrated high drug entrapment efficiency (75.1% ± 1.7%) and exceptional pH responsiveness, exhibiting up to 600% ± 3.0% swelling at pH 7.4 compared to pH 1.2 (109.5% ± 3.0%). Characterization by Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry-Thermogravimetric (DSC-TGA) analysis demonstrated successful complexation and inclusion of the complex into a thermally stable nanogel matrix. A sustained release profile was demonstrated by in vitro release studies, with 76.5% ± 4.5% cumulative release observed over 48 h, prolonging the retention interval relative to the unencapsulated control. Kinetic modeling demonstrated that the drug release mechanism adheres to anomalous (non-Fickian) transport (n = 0.68, R
2 = 0.95), indicating that release is actively influenced by both fusidic acid diffusion and the reversible swelling/deswelling of the N-Isopropylacrylamide-Itaconic acid (NIPAM-IA) polymer network in response to environmental stimuli (pH and temperature). This dual-responsive system provides a promising foundation for localized and regulated antibiotic administration. The synergistic pairing of enhanced solubility by cyclodextrin complexation and the smart sustained release mechanism provided by thermo- and pH-responsive nanogels offers significant possibilities to increase patient adherence and deal with antimicrobial resistance in the management of bacterial skin infections.