Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China.
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, 266021, China.
Drug Deliv Transl Res. 2021 Jun;11(3):1119-1132. doi: 10.1007/s13346-020-00834-0.
Nimodipine (NMD), a calcium channel blocker, has demonstrated benefits in treating glaucoma. However, its ocular therapeutic application remains limited due to its poor aqueous solubility, which restrains the development of an ophthalmic formulation. Thus, the present study aimed to formulate an NMD micelle ophthalmic solution to enhance the potential of NMD in an ocular topical formulation to treat glaucoma. The NMD micelle ophthalmic solution was formulated with nanocarriers composed of rebaudioside A and D-α-tocopheryl polyethylene glycol 1000 succinate. Spherical mixed micelles were optimized and obtained at a small micelle size 13.429 ± 0.181 nm with a narrow size distribution (polydispersity index 0.166 ± 0.023) and high encapsulation efficiency rate (99.59 ± 0.09%). Compared with free NMD, NMD in micelles had much greater in vitro membrane permeability and antioxidant activity. The NMD micelle ophthalmic solution was well tolerated in rabbit eyes. It profoundly improved the in vivo intraocular permeation of NMD, and in vivo intraocular pressure reduction and improved miosis were also observed. Accordingly, this NMD micelle ophthalmic solution might be a promising ocular formulation to treat glaucoma. Graphical abstract.
尼莫地平（NMD）是一种钙通道阻滞剂，已被证明对治疗青光眼有益。然而，由于其较差的水溶性，限制了其在眼部制剂中的应用，因此其眼部治疗应用仍然有限。因此，本研究旨在制备尼莫地平胶束滴眼溶液，以提高尼莫地平在眼部局部制剂治疗青光眼方面的潜力。尼莫地平胶束滴眼溶液由甜菊苷 A 和 D-α-生育酚聚乙二醇 1000 琥珀酸酯组成的纳米载体制成。优化并得到了球形混合胶束，其胶束粒径为 13.429 ± 0.181nm，粒径分布较窄（多分散指数为 0.166 ± 0.023），包封率高（99.59 ± 0.09%）。与游离尼莫地平相比，胶束中的尼莫地平具有更大的体外膜透过性和抗氧化活性。尼莫地平胶束滴眼溶液在兔眼内具有良好的耐受性。它显著提高了尼莫地平的体内眼内渗透，同时观察到眼压降低和瞳孔缩小改善。因此，这种尼莫地平胶束滴眼溶液可能是一种有前途的治疗青光眼的眼部制剂。
