a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China.
b Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences , Qingdao , China.
Drug Deliv. 2019 Dec;26(1):158-167. doi: 10.1080/10717544.2019.1568624.
The aim was to develop a nanocarrier based on polyoxyl 15 hydroxystearate (Kolliphor® HS15, HS15) micelles for the solubility, stability, and ocular delivery of myricetin (Myr). An optimized ratio of HS15 and Myr was prepared to fabricate HS15-Myr micelle ophthalmic solution. Myr-encapsulating HS15 micelles (HS15-Myr micelles) were subjected to physicochemical characterizations. The chemical stability of Myr in HS15 micelles and storage stability of HS15-Myr micelle ophthalmic solutions were evaluated. In vitro parallel artificial membrane permeability assay and antioxidant activity of Myr in HS15 micelles were also measured. In vivo ocular tolerance, corneal permeation, and anti-inflammatory efficacy studies were conducted following ocular topical administration. HS15-Myr micelles were successfully prepared and presented transparent appearance with high encapsulation (96.12 ± 0.31%), ultra-small micelle size (a mean diameter of 12.17 ± 0.73 nm), uniform size distribution (polydispersity index [PDI] = 0.137 ± 0.013), and negative surface charge (- [4.28 ± 0.42] mV). Myr in HS15 micelle solution demonstrated higher aqueous stability than the free Myr solution among the accepted pH range for eyedrops. HS15-Myr micelle ophthalmic solution demonstrated high storage stability at 4 °C and 25 °C. HS15 micelles could significantly improve in vitro antioxidant activity and faster membrane permeation of Myr. No irritations or corneal damage were revealed in rabbit eyes after ocular administration of HS15-Myr micelle solution. In vivo corneal permeation study demonstrated that HS15-Myr micelles could penetrate the cornea efficiently in mouse eyes. Further, HS15-Myr micelles also demonstrated significant in vivo anti-inflammatory activity. It can be concluded that HS15 micelles are a potential ophthalmic delivery nanocarrier for poorly soluble drugs such as Myr.
目的是开发一种基于聚氧乙烯 15 氢化蓖麻油（Kolliphor® HS15，HS15）胶束的纳米载体，以提高杨梅素（Myr）的溶解度、稳定性和眼部递药效率。制备了优化的 HS15 和 Myr 比例，以制备 HS15-Myr 胶束眼用溶液。对包封杨梅素的 HS15 胶束（HS15-Myr 胶束）进行理化性质表征。评估了 HS15 胶束中 Myr 的化学稳定性和 HS15-Myr 胶束滴眼剂的储存稳定性。还测量了 HS15 胶束中 Myr 的体外平行人工膜透过性和抗氧化活性。进行了眼部局部给药后的体内眼耐受性、角膜透过性和抗炎功效研究。成功制备了 HS15-Myr 胶束，呈透明外观，包封率高（96.12±0.31%），胶束粒径超小（平均直径为 12.17±0.73nm），粒径分布均匀（多分散指数[PDI]=0.137±0.013），带负电荷（-[4.28±0.42]mV）。在滴眼剂可接受的 pH 范围内，HS15 胶束溶液中的 Myr 比游离 Myr 溶液具有更高的水稳定性。HS15-Myr 胶束滴眼剂在 4°C 和 25°C 下具有高储存稳定性。HS15 胶束可显著提高 Myr 的体外抗氧化活性和更快的膜透过性。HS15-Myr 胶束溶液滴眼后，兔眼无刺激或角膜损伤。体内角膜透过性研究表明，HS15-Myr 胶束可有效穿透小鼠眼睛的角膜。此外，HS15-Myr 胶束还具有显著的体内抗炎活性。综上所述，HS15 胶束是一种具有潜力的眼部递药纳米载体，可用于递运杨梅素等水溶性差的药物。
