Abstract：
The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m-1) and viscosity (2.69 ± 0.15 mPa s-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.
摘要：
青光眼治疗的一线重点是通过局部前列腺素类似物的处方降低眼内压（IOP），如拉坦前列素（LAT）。局部眼用药物由于其从眼表快速消除而具有低生物利用度。纳米技术提供了提高抗青光眼剂的眼部生物利用度同时降低给药频率的创新方法。这项研究旨在将LAT负载的合成磷脂酰胆碱脂质体与透明质酸（0.2％w/v）和渗透保护剂甜菜碱（0.40％w/v）和亮氨酸（0.90％w/v）（LAT-HA-LIP）结合起来，以延长LAT的降压作用，同时保护眼表。LAT-HA-LIP制备为1,2-二油酰基-sn-甘油-3-磷酸胆碱和1,2-二肉豆蔻酰基-sn-甘油-3-磷酸胆碱的混合物，胆固醇和α-生育酚乙酸酯。LAT-HA-LIP具有较高的载药量(104.52±4.10%),单峰囊泡大小（195.14±14.34nm），ζ电位为-13.96±0.78mV。LAT-HA-LIP是等渗的（284.00±1.41mOsmL-1），具有中性pH（7.63±0.01），并具有合适的表面张力（44.07±2.70mNm-1）和粘度（2.69±0.15mPas-1），用于局部眼科给药。LAT-HA-LIP在人角膜和结膜上皮细胞中表现出最佳的体外耐受性。当将LAT-HA-LIP滴入白化病雄性新西兰兔中时，未观察到眼部改变或不适的迹象。低血压研究显示,一次滴眼液后，LAT-HA-LIP的作用持续时间比市售制剂长24小时，相对眼部生物利用度几乎高三倍（p<0.001）。这些发现表明LAT-HA-LIP在青光眼治疗中具有潜在的眼部保护和降压作用。
