Nanocubosomal based in situ gel loaded with natamycin for ocular fungal diseases: development, optimization, in-vitro , and in-vivo assessment

Abstract

Natamycin (NT) is a synthetic broad-spectrum antifungal used in eye drops. However, it has low solubility and high molecular weight, limiting its permeation, and generally causes eye discomfort or irritation when administered. Therefore, the present study aimed to develop an ophthalmic in situ gel formulation with NT-loaded cubosomes to enhance ocular permeation, improve antifungal activity, and prolong the retention time within the eye. The NT-loaded cubosome (NT-Cub) formula was first optimized using an I-optimal design utilizing phytantriol, PolyMulse, and NT as the independent formulation factors and particle size, entrapment efficiency %, and inhibition zone as responses. Phytantriol was found to increase particle size and entrapment efficiency %. Higher levels of PolyMulse slightly increased the inhibition zone whereas a decrease in particle size and EE% was observed. Increasing the NT level initially increased the entrapment efficiency % and inhibition zone. The optimized NT-Cub formulation was converted into an in situ gel system using 1.5% Carbopol 934. The optimum formula showed a pH-sensitive increase in viscosity, favoring prolonged retention in the eye. The in vitro release of NT was found to be 71 ± 4% in simulated tear fluid. The optimum formulation enhanced the ex vivo permeation of NT by 3.3 times compared to a commercial formulation and 5.2 times compared to the NT suspension. The in vivo ocular irritation test proved that the optimum formulation is less irritating than a commercial formulation of NT. This further implies that the developed formulation produces less ocular irritation and can reduce the required frequency of administration.

Novel Eye Drop Delivery Systems: Advance on Formulation Design Strategies Targeting Anterior and Posterior Segments of the Eye

“…Also importantly, it was easy to perfuse and reduced the frequency of perfusion, thus making it more acceptable to the patient [96]. Table 3 [93][94][95][96][97][98][99] lists pH-sensitive in situ gel eye drop delivery systems in the application of the anterior and posterior segments of the eye.…”

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia

“…The flow rate of the mobile phase was performed at 1 mL/min, and the FI was eluted at 3.4 min. The steady-state flux (Jss) for each sample was calculated using the slope of the curve plot between the cumulative percentage penetrated and time (Hosny et al., 2021 ).…”

Cubosomes as an emerging platform for drug delivery: a review of the state of the art

“…Stability studies were conducted after synthesis of the cubosomes and after 96 h, and there was no significant difference in the PDI or zeta potential during this period. Relative to the impact of single-component cubosomes composed of DOX DOTAGA-OA or DOTAGA-OA- 177 Lu complexes, cubosomes combining doxorubicin and the radionuclide-based complexes showed significant cellular toxicity as evaluated by the vitality of the in vitro HeLa cell lines. The stability of the cubosomes with 177 Lu was studied in PBS buffer and human serum for 24 h, and up to 86% and 78% radioactivity, respectively, was retained in the cubosomes.…”

“…In comparison with the market product Alphagan s P, the in vivo analysis revealed a 4.6-fold higher AUC and a 9.1-fold rise in the mean residence time. 176 Additional studies that showed significant results include a natamycin/cubosome in situ gel, 177 a ketoconazole/cubosome gel, 178 fluconazole/cubosomal nanoparticles, 179 acetazolamide/ cubosomes, 180 dorzolamide/cubogel, 181 and latanoprost/ cubosomes. 182…”

“…Thus the folate-modified ETP-containing cubosomes could be a potential anti-cancer drug-delivery system. 209 In a pioneering study, cubosomes were employed as a dualmodality cargo carrier for systemic radiation and cancer therapy in a study by Cytryniak et al The chemotherapeutic medication doxorubicin and a routinely used radio-isotope, the low-energy beta (b À )-emitting nuclide 177 Lu, were loaded into monoolein (GMO)-based cubosomes. The radio-isotope was combined with a DOTAGA-derived congener (DOTAGA-OA).…”