Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 130, Issue -, Pages 148-157Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2019.02.092
Keywords
Metronidazole; Mucoadhesion; Thiolated polymer; Thiomers; Vaginal drug delivery
Funding
- Higher Education Commission of Pakistan (HEC)
- Austrian Agency for International Cooperation in Education and Research (OAD)
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The aim of this study was to synthesize novel polymeric excipients forming mucoadhesive films for treatment of vaginal microbial infections. 2-(2-Amino ethyldisulfanyl) nicotinic acid was conjugated with gellan gum via amide bond formation. The structure of the resulting S-protected gellan gum was confirmed by 1H NMR. S protected gellan gum variants were characterized for thiol content, cytotoxicity, rheological behaviour and film forming capability. Depending on the added amount of AMENA degree of thiolation was 81 13 (S-GG 81) and 174 + 16 (S-GG 174) pmol/g, respectively. Vaginal films were casted from S-protected gellan gum variants and studied for adherence to vaginal mucosa, drug release and antimicrobial activity. S-protected gellan gum remained biocompatible showing >87% cell viability. S-GG 81 and S-GG 174 exhibited 1.84- and 4.3-fold increased dynamic viscosity in porcine mucus in comparison to unmodified gellan gum, respectively. Compared to gellan gum films, thiol functionalized gellan gum films showed 3-fold improved adhesion on mucosal surface over a period of 3 h along with significant antimicrobial activity. Moreover, S-protected gellan gum provided a sustained release of metronidazole. According to these results, S-protected gellan gum proved to be a promising novel excipient for casting vaginal films, exhibiting strongly improved mucoadhesive and antimicrobial properties. (C) 2019 Elsevier B.V. All tights reserved.
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