title: Development of Timolol-Loaded Galactosylated Chitosan Nanoparticles and Evaluation of Their Potential for Ocular Drug Delivery.
abstract: This study was conducted to develop timolol maleate (TM)-loaded galactosylated chitosan (GC) nanoparticles (NPs) (TM-GC-NPs) followed by optimization via a four-level and three-factor Box-Behnken statistical experimental design. The optimized nanoparticles showed a particle size of 213.3 ± 6.83 nm with entrapment efficiency of 38.58 ± 1.31% and drug loading of 17.72 ± 0.28%. The NPs were characterized with respect to zeta potential, pH, surface morphology, and differential scanning calorimetry (DSC). The determination of the oil-water partition coefficient demonstrated that the TM-GC-NPs had a high liposolubility at pH 6 as compared to timolol-loaded chitosan nanoparticles (TM-CS-NPs) and commercial TM eye drops. The in vitro release study indicated that TM-GC-NPs had a sustained release effect compared with the commercial TM eye drops. Ocular tolerance was studied by the hen's egg chorioallantoic membrane (HET-CAM) assay and the formulation was non-irritant and could be used for ophthalmic drug delivery. The in vitro transcorneal permeation study and confocal microscopy showed enhanced penetration, and retention in the cornea was achieved with TM-GC-NPs compared with the TM-CS-NPs and TM eye drops. Preocular retention study indicated that the retention of TM-GC-NPs was significantly longer than that of TM eye drops. The in vivo pharmacodynamic study suggested TM-GC-NPs had a better intraocular pressure (IOP) lowering efficacy and a prolonged working time compared to commercial TM eye drops (P ≤ 0.05). The optimized TM-GC-NPs could be prepared successfully promising their use as an ocular delivery system.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Zhengzhou University, 100 Kexue Dadao, Zhengzhou, 450001, Henan, People's Republic of China.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Qilu Pharmaceutical Co., Ltd., Jinan, Shandong, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Zhengzhou University, 100 Kexue Dadao, Zhengzhou, 450001, Henan, People's Republic of China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Zhengzhou University, 100 Kexue Dadao, Zhengzhou, 450001, Henan, People's Republic of China.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Zhengzhou University, 100 Kexue Dadao, Zhengzhou, 450001, Henan, People's Republic of China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Zhengzhou University, 100 Kexue Dadao, Zhengzhou, 450001, Henan, People's Republic of China. liuweiyxy@zzu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning / Q000379:methods; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D003315:Cornea; D016503:Drug Delivery Systems; D007429:Intraocular Pressure / Q000187:drug effects; D053758:Nanoparticles; D010316:Particle Size; D011817:Rabbits; D013999:Timolol / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D001672:Biocompatible Materials; D013999:Timolol; D048271:Chitosan
keywords: galactosylated chitosan; nanoparticle; ocular delivery; timolol