Formulation of Piperine-Loaded Nanoemulsion: In Vitro Characterization, Ex Vivo Evaluation, and Cell Viability Assessment.

Piperine is an alkaloid, but its therapeutic efficacy is limited due to poor aqueous solubility. In this study, piperine nanoemulsions were prepared using oleic acid (oil), Cremophore EL (surfactant), and Tween 80 (co-surfactant) using the high-energy ultrasonication approach. The optimal nanoemulsion (N2) was further evaluated using transmission electron microscopy, release, permeation, antibacterial, and cell viability studies based on minimal droplet size and maximum encapsulation efficiency. The prepared nanoemulsions (N1-N6) showed a transmittance of more than 95%, a mean droplet size between 105 ± 4.11 and 250 ± 7.4 nm, a polydispersity index of 0.19 to 0.36, and a ζ potential of -19 to -39 mV. The optimized nanoemulsion (N2) showed significantly improved drug release and permeation compared with pure piperine dispersion. The nanoemulsions were stable in the tested media. The transmission electron microscopy image showed a spherical and dispersed nanoemulsion droplet. The antibacterial and cell line results of piperine nanoemulsions were significantly better than the pure piperine dispersion. The findings suggested that piperine nanoemulsions may be a more advanced nanodrug delivery system than conventional ones.

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

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.