a Department of Pharmaceutics, School of Pharmacy , Hamadan University of Medical Sciences , Hamadan , Iran.
b Drug Delivery Research Group, School of Science , Auckland University of Technology , Auckland , New Zealand.
Pharm Dev Technol. 2019 Jun;24(5):600-606. doi: 10.1080/10837450.2018.1547748. Epub 2019 Jan 15.
The aim of this study was to investigate the corneal penetration of brinzolamide (BZ) nanoemulsions (NEs) and evaluate their in vitro and ex vivo irritancy potential. Twelve BZ NEs were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the Hen's Egg Test-Chorio-Allantoic Membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven BZ NEs exhibited superior penetration across isolated bovine cornea compared to the marketed BZ suspension. The half maximal inhibitory concentration (IC) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not result in any irritation and were thus considered safe for ocular use. Our finding suggests that optimized NEs can be a safe and effective vehicle for ocular delivery of BZ.
本研究旨在考察布林佐胺（BZ）纳米乳（NE）的角膜穿透性，并评估其体外和离体刺激性。采用自发乳化法制备了 12 种 BZ NE，并将其固定在 Franz 扩散池上的离体牛角膜上进行体外渗透研究。为了确认制剂用于眼部的安全性，使用视网膜细胞活力测定法、鸡胚绒毛尿囊膜（HET-CAM）和牛角膜混浊-通透性（BCOP）试验对制剂进行了潜在眼刺激性检查。与市售 BZ 混悬剂相比，7 种 BZ NE 在分离的牛角膜中的穿透性更好。使用视网膜细胞的磺基罗丹明 B 细胞活力测定法测定各种表面活性剂和油的半最大抑制浓度（IC）值表明，Transcutol P、Cremophor RH40 和三醋酸甘油酯是毒性最小的赋形剂，可在各种浓度下安全用于眼部。HET-CAM 和 BCOP 试验表明，NE6B 和 NE4C 不会引起任何刺激，因此被认为可安全用于眼部。我们的研究结果表明，优化的 NE 可以成为眼部递药布林佐胺的安全有效载体。
