Nasal mucoadhesive in situ gelling liquid crystalline fluid precursor system of polyene antibiotic for potential treatment of localized sinuses aspergillosis post COVID infection

Abstract

Nasal mucoadhesive in situ gelling liquid crystalline precursor system (IGFPS) of nystatin was developed for localized treatment of nasal aspergillosis post COVID infection. The stimuli-sensitive sol system comprising of Monoolein (60%w/w), Oleic acid (10%w/w), Dimethyl sulfoxide (15%w/w), Poloxamer 407 (9%w/w), and the drug (2.23%w/w) exhibited a faster sol–gel transformation in situ with good swelling ability. The small angle X-ray scattering study identified the coexistence of Im3m cubic phase with hexagonal closed pack P63/mmc structures. The subzero differential scanning calorimetry studies identified entrapped interphasal water and free water in the gels with confirmation of gelation due to micellization. Mucoadhesive properties of the gel indicate these systems to prolong the residence time at the site of absorption. The gels followed Non-Newtonian flow pattern characteristic of pesudoplastic type. The oscillatory rheology revealed that high complex viscosity and lower tanδ value provided superior adhesiveness and mucoadhesion ability to the gel. The gel exhibited a drug release of 86% at the end of 8h and of Higuchi kinetics with anomalous transport. The IGFPS exhibited better in vitro antifungal activity in comparison to drug solution. The system demonstrated permeation enhancing effect undamaged cilia and no serious histological changes. Post intranasal administration the maximum concentration (11.79 ± 2.31 μg/ml) was realized in 20 min and the curve showed a decline similar to intravenous. The storage stability of the IGFPS was found to be within acceptable limits for stability. Thus, a nasal mucoadhesive in situ gelling fluid liquid crystalline precursor formulation may represent a promising novel alternative for the localized and systemic delivery of nystatin.

GRAPHICAL ABSTRACT

Keywords:

• Nystatin
• polyene antibiotic
• in situ gelling fluid precursor system (IGFPS)
• nasal
• aspergillosis
• COVID