Overcoming corneal barriers: Posaconazole loaded cationic surfactant vesicles for enhanced ocular permeability and anti-fungal efficacy

Abstract

Posaconazole (PCZ) is a broad-spectrum anti-fungal drug approved by FDA and currently used off-label for the treatment of fungal keratitis (FK). Although ocular route serves as the most bioavailable route for treating FK, delivery of PCZ to the eye remains a challenge due to poor permeation though the cornea and rapid elimination from the eye. Here we outline a comprehensive formulation development process, beginning with in silico studies, progressing through in vitro evaluations, and ultimately achieving therapeutic benefits in vivo. We report modified niosome-like surfactant vesicles, hereafter termed as NioTherms, formulated using a novel and simple heat-mix method, encapsulating PCZ for ocular administration in the form of an in situ gel. Excipient screening performed using in silico simulations highly correlate with in vitro studies ( $180.7\pm 2.3\text{ }\mathrm{n}\mathrm{m}$ ), guiding optimization by Quality by Design (QbD) approach for encapsulating PCZ in NioTherms resulting in particles with an average size of $+27.5\pm 2.2\mathrm{m}\mathrm{V}$, zeta potential of $87.6\mathrm{\%}\pm 1.7\mathrm{\%}$ and entrapment efficiency of. A 2 -fold increase in both mucin binding and cellular uptake indicates a functional role of positive surface charge in enhancing mucoadhesive properties of PCZ-NioTherms. In an in vivo murine ocular keratitis model, we demonstrate a 2 -fold enhancement in trans-corneal permeability of PCZ-NioTherms and a 3 -fold reduction in fungal burden compared to the control standard of care, the PCZ solution. Owing to a facile formulation process, we anticipate that PCZ-NioTherms would serve as a clinically translatable and patient compliant therapeutic intervention for treating FK.

Keywords

Posaconazole / Surfactant vesicles / Cationic / Mucoadhesive / Ocular / Fungal keratitis

Conflicts of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Acknowledgements

The authors would like to acknowledge Dr. V. K. Aswal and Dr. Sugam Kumar from Bhabha Atomic Research Centre (BARC), Mumbai, India for providing facility to conduct Small Angle Neutron Scattering (SANS) studies.

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajps.2025.101087. The figures and tables with " S " before the serial number are included in the Supplementary material.

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