The alkaline milieu of chronic wounds severely impairs the therapeutic effect of antibiotics, such as rifampicin; as such, the development of new drugs, or the smart delivery of existing drugs, is required. Herein, two innovative polyelectrolyte nanoparticles (PENs), composed of an amphiphilic chitosan core and a polycationic shell, were synthesized at alkaline pH, and in vitro performances were assessed by 1H NMR, elemental analysis, FT-IR, XRD, DSC, DLS, SEM, TEM, UV/Vis spectrophotometry, and HPLC. According to the results, the nanostructures exhibited different morphologies but similar physicochemical properties and release profiles. It was also hypothesized that the simultaneous use of the nanosystem and an antioxidant could be therapeutically beneficial. Therefore, the simultaneous effects of ascorbic acid and PENs were evaluated on the release profile and degradation of rifampicin, in which the results confirmed their synergistic protective effect at pH 8.5, as opposed to pH 7.4. Overall, this study highlighted the benefits of nanoparticulate development in the presence of antioxidants, at alkaline pH, as an efficient approach for decreasing rifampicin degradation.

Centre of Polymer Systems University Institute TBU tr Tomase Bati 5678 76001 Zlin Czech Republic

Department of Chemistry Faculty of Technology TBU Vavrečkova 275 76001 Zlín Czech Republic

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Ke Karlovu 455 2 12808 Prague 2 Czech Republic

iMed ULisboa Faculty of Pharmacy Universidade de Lisboa 169 003 Lisbon Portugal

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