Fungal keratitis, a noxious disease that could cause vision loss, is difficult to treat and requires frequent eye drop administration. Low bioavailability of topical formulae eye drops, typically ~2 to 5%, leads to the need for high frequency dosing, resulting in low patient compliance. Continuous drug delivery with a contact lens could be an alternative to eye drops to enhance bioavailability significantly while simultaneously increasing patient compliance. Mesoporous silica nanoparticles (MSN), as a drug carrier candidate, has broad potential for chemical modifications and tunable textural properties. Encapsulating drugs into MSN provides a way to enhance solubility and hence bioavailability.<br/>We aim to impregnate the antifungal medication, voriconazole, into MSN and embed it into an antimicrobial chitosan matrix to investigate its potential for antifungal drug delivery. We found that, while loading voriconazole via immersion adsorption onto MSN results in low drug content (&lt;3 wt%), another loading method — solvent evaporation — can yield a higher loading of 29 wt%. The release profile of voriconazole (Fig.1) from 29 wt% drug-loaded MSN shows faster complete release compared to drug particles as received, indicating enhanced solubility.<br/>We wish to study the physical form of the voriconazole adsorbed onto or into the MSN particles. Thermogravimetric analysis of drug-loaded MSN shows that encapsulated voriconazole has a lower degradation onset temperature of 145.2 °C compared to 160.4 °C as received, suggesting that the voriconazole may have been sequestered into the small pores of MSN in an amorphous form. The embedment of MSN into chitosan was successful. In the contact lens device chitosan as matrix will serve a dual function as 1) a diffusion barrier to the drug delivery to extend the release, and 2) further prevent fungal growth on the lens surface. This composite drug delivery system can potentially serve as the basis for daily or two-day disposal contact lenses for fungal keratitis treatment.

Enhanced solubility of poorly soluble voriconazole with mesoporous silica towards antifungal ocular drug delivery

ACS Fall 2021

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