School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road Higher Education Mega Center, Guangzhou, Guangdong, 510006, China.
Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China.
AAPS PharmSciTech. 2017 Nov;18(8):2919-2926. doi: 10.1208/s12249-017-0763-8. Epub 2017 Apr 20.
Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization. These constructed nanoparticles appeared spherical using transmission electron microscopy and had an average particle size of 142 nm, zeta potential of -6.27 mV, and over 85% encapsulation efficiency. Moreover, using polarized light microscopy and small-angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic liquid crystalline D-type (Pn3m) structure, which provides good physicochemical stability and high encapsulation efficiency. Ex vivo corneal permeability experiments showed that the total amount of TM cubosomes penetrated was higher than the commercially available eye drops. In addition, in vivo studies revealed that TM cubosomes reduced the IOP in rabbits from 27.8∼39.7 to 21.4∼32.6 mmHg after 1-week administration and had a longer retention time and better lower-IOP effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor histological impairment in the rabbit corneas was observed. This study suggests that cubosomes are capable of increasing the corneal permeability and bioavailability of TM and have great potential for ocular disease treatment.
青光眼是一种以眼内压（IOP）升高为特征的眼病，其主要治疗策略是通过药物降低 IOP。目前，治疗青光眼的眼部药物输送面临着多种挑战，例如由于人眼的独特解剖结构，角膜通透性和生物利用度低。为了应对这些挑战，本研究构建了用于马来酸噻吗洛尔（TM）的立方体制剂药物输送系统治疗青光眼。TM 立方体制剂（液晶纳米颗粒）是通过高压匀质法用甘油单油酸酯和泊洛沙姆 407 制备的。透射电子显微镜显示这些构建的纳米颗粒呈球形，平均粒径为 142nm，zeta 电位为-6.27mV，包封效率超过 85%。此外，使用偏光显微镜和小角 X 射线散射（SAXS）表明，TM 立方体制剂具有立方液晶 D 型（Pn3m）结构，提供了良好的物理化学稳定性和高包封效率。离体角膜通透性实验表明，TM 立方体制剂穿透的 TM 总量高于市售眼药水。此外，体内研究表明，TM 立方体制剂在给药 1 周后将兔子的 IOP 从 27.8∼39.7mmHg 降低至 21.4∼32.6mmHg，并且具有比市售 TM 眼药水更长的保留时间和更好的降眼压效果。此外，兔眼角膜既没有观察到细胞毒性也没有组织学损伤。本研究表明，立方体制剂能够增加 TM 的角膜通透性和生物利用度，在眼部疾病治疗方面具有巨大潜力。
