The
aim of this study
was to synthesize
polymeric excipients that can form mucoadhesive hydrogels containing
amphotericin B (AmB) for the treatment of mucosal leishmaniasis. 2-(2-Acryloylaminoethyldisulfanyl)-nicotinic
acid (ACENA) was copolymerized with N-vinyl pyrrolidone
to obtain thiolated polyvinylpyrrolidone (PVP) that was then complexed
with AmB to improve its solubility. The resulting structure of thiolated
PVP was evaluated by 1H nuclear magnetic resonance to confirm
S-protected thiol groups, and the average molecular mass was determined
by size exclusion chromatography. Moreover, variants of thiolated
PVP–AmB were studied for the thiol content, amount of complexed
AmB, cytotoxicity, mucoadhesive properties, and antileishmaniasis
activity. The highest achieved degree of thiolation was 772 ±
24.64 μmol/g, and the amount of complexed AmB was 27.05 ±
0.31 μmol per g of polymer. Thiolated PVP and thiolated PVP–AmB
variants (0.5% m/v) showed no cytotoxicity, whereas the equivalent
concentration of free AmB reduced Caco-2 cell viability to 70% within
24 h. Thiol-functionalized PVP and PVP–AmB complexes displayed
7.66- and 7.20-fold higher adhesion to the mucosal surface in comparison
to unmodified PVP and PVP–AmB, respectively. In addition, variants
of thiolated PVP–AmB complexes displayed 100% antileishmaniasis
activity in comparison to the 80% killing efficiency of Fungizone,
which has been applied in the equivalent AmB concentration of 0.2
μg/mL. Thiol-functionalized PVP proved to be a promising novel
excipient for the delivery of AmB providing enhanced solubility and
improved mucoadhesive properties which are beneficial for the treatment
of mucosal leishmaniasis.