Development of Timolol-Loaded Galactosylated Chitosan Nanoparticles and Evaluation of Their Potential for Ocular Drug Delivery

作者：Zhao, Ruobing; Li, Jing; Wang, Jingyi; Yin, Zhenya; Zhu, Yongtao; Liu, Wei^*

来源：AAPS PHARMSCITECH, 2017, 18(4): 997-1008.

DOI：10.1208/s12249-016-0669-x

• galactosylated chitosan
• nanoparticle
• ocular delivery
• timolol

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-CSNPs) 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.

• 出版日期2017-5
• 单位郑州大学