Triple-action mesoporous silica nanoparticle-chitosan composite contact lens design towards ocular infection treatment

Fungal keratitis is a severe sight-threatening ocular infection that has over 1 million new cases globally each year. The current clinical standard of care involves frequent eye drop administration, which results in low patient compliance. The root of the need for frequent dosing of eye drops lies in low bioavailability of 2-5% due to rapid tear drainage and low drug solubility. Using contact lens as an alternative drug delivery vehicle can increase bioavailability by up to 50%. Recently, we have shown that some polymeric nanopillar surfaces can have excellent antimicrobial properties. Taking advantage of both, we explored a composite system with antimicrobial nanopillar surface to serve as a triple-action contact lens.
The composite contact lens system consists of three components to combat fungi: nanoparticle loaded with drugs, an inherently antifungal biopolymer matrix, chitosan, and nanopillars on the lens surface. We impregnated an antifungal medication –– voriconazole –– into mesoporous silica nanoparticles (MSN) and embedded these particles into the chitosan matrix. The drug content in voriconazole loaded MSN (MSN-VRZ) is verified with thermogravimetric analysis to be 28.5 %. The drug release from the MSN-VRZ composite reached a plateau at 4 h regardless of the existence of nanopatterns, while drug release from voriconazole directly loaded into the chitosan film completed release at 8 h. The DSC result of MSN-VRZ reveals the coexistence of a board glass transition peak and a melting temperature that is lower compared to pristine voriconazole. These results indicate that voriconazole is in both amorphous and crystalline forms, though in smaller sizes than the pristine voriconazole in our starting material. These observations may explain the rapid dissolution behavior. The in vitro fungal killing efficacy assay showed that the drug release from composite is capable of inhibiting fungi until t= 4 h for both aspergillus and fusarium. The light transmittance of the composite with nanopillar (86%) is comparable to the commercial contact lens (83.9%). The synergy effect between nanopillar and drug for fungi inhibition will also be discussed. Overall, this composite system shows a promising design for a drug delivering contact lens to treat fungal keratitis.