Ocular cationic nanocarrier-based delivery of posaconazole

Ocular fungal keratitis cases are rising globally, especially in immunocompromised patients. Ocular barriers including corneal epithelium and tear turnover, limit drug delivery and treatment efficacy. In view of this, an advanced cationic nanocarrier formulation system offers a promising approach to overcome these challenges. Posaconazole-loaded cationic nanocarrier formulation system (leciplex) was fabricated using soy phosphatidylcholine, didodecyl dimethyl ammonium bromide and Transcutol HP by one-step fabrication technique. A 3² full factorial design was applied to optimize responses such as particle size, entrapment efficiency and zeta potential. Leciplex displayed spherical shape with small particle size of 162.5±3.4nm to avoid irritation to the ocular portion, high entrapment efficiency (97.7±1.8%) to load minimal quantity of leciplex formulation, and positively charged zeta potential +62.5mV to interact with negatively charged ocular mucin layer. In vitro permeation studies revealed sustained drug permeation profile. Ex vivo corneal retention analysis demonstrated 45.6% drug retention, thus suggested prolonged ocular residence. The strong binding between posaconazole leciplex and mucin was assured by mucoadhesion study. Further, prolonged drug permeation of leciplex compared to drug solution was confirmed by performing permeation study through isolated goat cornea. Next, higher corneal retention of leciplex favoured treatment of fungal infection at corneal site. Isolated chicken eye test exhibited no irritation or toxicity thus confirmed ocular safety and biocompatibility of leciplex. Antifungal activity against Candida albicans revealed significantly enhanced efficacy compared to drug solution. Thus, posaconazole-loaded cationic leciplex efficiently delivered posaconazole to the corneal surface, where it adhered to the anionic mucosal layer through electrostatic interactions.