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, 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 (R²=0.77), guiding the optimization by Quality by Design (QbD) approach for encapsulating PCZ in NioTherms resulting in particles with an average size of 180.7 ± 2.3 nm, zeta potential of +27.5 ± 2.2 mV and entrapment efficiency of 87.6% ± 1.7%. A 2-fold increase in both mucin binding and cellular uptake indicate 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.

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Materials

PCZ was obtained as a gift sample from Bajaj Healthcare Ltd. (Thane, India). Transcutol P was provided as a gift sample from Gattefosse (Mumbai, India). Tween 80, Tween 85, Span 20, Span 60, dicetyl phosphate (DCP), Type III porcine mucin, sodium lauryl sulphate (SLS) and rhodamine B (RhB) were obtained from Sigma-Aldrich (Mumbai, India). Cremophor EL, 2-pyrrolidone and poloxamer 407 were procured from BASF (Mumbai, India). Polyethylene glycol 400 (PEG), propylene Glycol (PG), cholesterol and dimethyl sulfoxide (DMSO) were purchased from SDFCL (India). Stearylamine was purchased from SRL laboratories. Lactose, dextrose, sucrose, mannitol and trehalose were obtained from Signet Chemical Corporation (India). Sabouraud dextrose agar (SDA) media and broth were purchased from Hi-Media (India).

Kshitija M. Phatak, Ankita N. Yawalkar, Sushant S. Sole, Pradeep R. Vavia, Overcoming corneal barriers: Posaconazole loaded cationic surfactant vesicles for enhanced ocular permeability and anti-fungal efficacy, Asian Journal of Pharmaceutical Sciences, 2025, 101087, ISSN 1818-0876, https://doi.org/10.1016/j.ajps.2025.101087.

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