Dosmar Emily, Vuotto Gabrielle, Su Xingqi, Roberts Emily, Lannoy Abigail, Bailey Garet J, Mieler William F, Kang-Mieler Jennifer J
Department of Biology and Biomedical Engineering, Rose-Hulman Institute of Technology, 5500 Wabash Avenue, Terre Haute, IN 47803, USA.
Department of Biomedical Engineering, Illinois Institute of Technology, 10 W 35th St., Chicago, IL 60616, USA.
Pharmaceutics. 2021 Nov 4;13(11):1862. doi: 10.3390/pharmaceutics13111862.
The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery system (DDS) using a computational model and a 3D model of the eye. Hydrogel DDSs loaded with vancomycin (VAN) were synthesized and release behavior was characterized in vitro. Four different compartmental and four COMSOL models of the eye were developed to describe transport into the vitreous originating from a DDS placed topically, in the subconjunctiva, subretinally, and intravitreally. The concentration of the simulated DDS was assumed to be the initial concentration of the hydrogel DDS. The simulation was executed over 1500 and 100 h for the compartmental and COMSOL models, respectively. Based on the MATLAB model, topical, subconjunctival, subretinal and vitreous administration took most (~500 h to least (0 h) amount of time to reach peak concentrations in the vitreous, respectively. All routes successfully achieved therapeutic levels of drug (0.007 mg/mL) in the vitreous. These models predict the relative build-up of drug in the vitreous following DDS administration in four different points of origin in the eye. Our model may eventually be used to explore the minimum loading dose of drug required in our DDS leading to reduced drug use and waste.
本研究的目的是使用计算模型和眼部三维模型,研究水凝胶药物递送系统(DDS)中抗生素药物的转运情况。合成了负载万古霉素(VAN)的水凝胶DDS,并对其体外释放行为进行了表征。开发了四种不同的眼部房室模型和四种COMSOL模型,以描述药物从局部、结膜下、视网膜下和玻璃体内放置的DDS转运至玻璃体的情况。模拟的DDS浓度假定为水凝胶DDS的初始浓度。房室模型和COMSOL模型的模拟时间分别为1500小时和100小时。基于MATLAB模型,局部、结膜下、视网膜下和玻璃体给药分别在玻璃体中达到峰值浓度所需的时间最多(约500小时)至最少(0小时)。所有给药途径均成功在玻璃体中达到了治疗药物水平(0.007mg/mL)。这些模型预测了在眼部四个不同起始点给予DDS后药物在玻璃体中的相对蓄积情况。我们的模型最终可能用于探索我们的DDS中所需的最小药物负载剂量,从而减少药物使用和浪费。