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

Drug Delivery

Hala M. Alkhalidi¹  Amani M. El Sisi²  Sultan Alshehri³  Adel F. Alghaith³  Walaa A. Abualsunun⁴  Rana B. Bakhaidar⁴  Alshaimaa M. Almehmady⁴  Khaled M. Hosny⁵  Waleed Y. Rizg⁵ 

[1] Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabi;Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni -Suef, Egyp;Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabi;Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabi;Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabi;Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabi;

关键词: Cubosomes;    cornea;    in situ;    keratitis;    natamycin;    permeation;    phytantriol;   

DOI  :  10.1080/10717544.2021.1965675

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY