Development and Optimization of Hyaluronic Acid-Poloxamer In-Situ Gel Loaded with Voriconazole Cubosomes for Enhancement of Activity against Ocular Fungal Infection

Abstract

Fungal eye infections are largely disseminated, especially in developing countries where they may leave over half a million people blind per year. The current study aims to boost the voriconazole antifungal efficiency via loading it as cubosomes (VZ-Cub) into hyaluronic acid and poloxamer-based ocular in situ gel. VZ-Cub were fabricated applying Box-Behnken design and employing phytantriol, poloxamer F127, and VZ amounts as independent variables. The produced nano vesicles were evaluated for the dependent variables of particle size (PS), entrapment efficiency (EE%), and transcorneal steady-state flux (Jss) of the VZ, and, the obtained optimal VZ-Cub was loaded into an in situ gel base to enhance its ocular residence time. The in situ gel formulation was tested for its gelation temperature, drug release behavior, transcorneal permeation effects, and antifungal activity. The optimized VZ-Cub consisted of 100 mg of phytantriol, 60 mg of poloxamer F127, and 21 mg of VZ. This formulation led to a minimum PS of 71 nm, an EE% of 66%, Jss value of 6.5 µg/(cm2·min), and stability index of 94 ± 2%. The optimized VZ-Cub-loaded in situ gel released 84% VZ after 12 h and yielded a 4.5-fold increase in drug permeation compared with the VZ aqueous dispersion. The antifungal activity, which was obtained by measuring the fungal growth inhibition zones, revealed that the VZ-Cub-loaded in situ gel formulation had a 3.89-fold increase in antifungal activity compared with the VZ dispersion. In summary, an ocular in situ gel loaded with VZ-Cub could be an effective novel nano-paradigm with enhanced transcorneal permeation and antifungal properties.

Calcitermin-Loaded Smart Gels Activity against Candida albicans: A Preliminary In Vitro Study

“…Remarkably, an increased antifungal activity by gel inclusion has been shown for several potential antifungal compounds other than Cal, confirming our present findings [57][58][59][60][61][62][63][64]. For instance metal ions [58], and conventional fungicides such as miconazole and voriconazole, showed an increased action by gel inclusion also in vivo, in animal models [62,64].…”

Carbon Nanotube Hybrid Materials: Efficient and Pertinent Platforms for Antifungal Drug Delivery

“…through routes such as intravenous, topical, and more. [3,15,32,35,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Their antifungal activities have been investigated against a diverse range of fungal species like Candida albicans, Candida tropicalis, Aspergillus flavus, Aspergillus niger, Cryptococcus tropicum, Trichophyton rubrum, Microsporum canis, Aspergillus nidulans, Microsporum gypseum, Microsporum canis, Trichophyton mentagrophytes, Saccharomyces cerevisiae, and others [3,15,32,35,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] (Table 1).…”

Molecular Dynamics-Assisted Design of High Temperature-Resistant Polyacrylamide/Poloxamer Interpenetrating Network Hydrogels

“…When returned to a room temperature of 25 • C, the composite system returned to its original clear and transparent state. It has been reported that poloxamer will appear cloudy and gelatinized at high temperature [52,53], which may be beneficial to the stabilization of NPAM/poloxamer. Therefore, this facilely prepared blended hydrogel is expected to be used to improve the application range of polyacrylamide, especially in high temperature environments.…”