Physicochemical properties and micro-interaction between micro-nanoparticles and anterior corneal multilayer biological interface film for improving drug delivery efficacy: the transformation of tear film turnover mode
Huamei Li,
Fuda Dai,
Hanyu Liu,
Qi Tao,
Jie Hu,
Yangrong Zhang,
Zhenping Xiao,
Ilva D. Rupenthal,
Huihui Li,
Fan Yang,
Wei Li,
Huaqing Lin,
Dongzhi Hou
Affiliations
Huamei Li
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Fuda Dai
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Hanyu Liu
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Qi Tao
CAS Key Laboratory of Mineralogy and Metallogeny & Guangdong Provincial Key Laboratory of Mineral Physics and Materials, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences (CAS), Guangzhou, P.R. China
Jie Hu
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Yangrong Zhang
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Zhenping Xiao
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Ilva D. Rupenthal
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Huihui Li
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Fan Yang
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Wei Li
Guangzhou Institute for Drug Control, Guangzhou, P.R. China
Huaqing Lin
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Dongzhi Hou
Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
AbstractRecently, various novel drug delivery systems have been developed to overcome ocular barriers in order to improve drug efficacy. We have previously reported that montmorillonite (MT) microspheres (MPs) and solid lipid nanoparticles (SLNs) loaded with the anti-glaucoma drug betaxolol hydrochloride (BHC) exhibited sustained drug release and thus intraocular pressure (IOP) lowering effects. Here, we investigated the effect of physicochemical particle parameters on the micro-interactions with tear film mucins and corneal epithelial cells. Results showed that the MT-BHC SLNs and MT-BHC MPs eye drops significantly prolonged the precorneal retention time due to their higher viscosity and lower surface tension and contact angle compared with the BHC solution, with MT-BHC MPs exhibiting the longest retention due to their stronger hydrophobic surface. The cumulative release of MT-BHC SLNs and MT-BHC MPs was up to 87.78% and 80.43% after 12 h, respectively. Tear elimination pharmacokinetics study further confirmed that the prolonged precorneal retention time of the formulations was due to the micro-interaction between the positively charged formulations and the negatively charged tear film mucins. Moreover, the area under the IOP reduction curve (AUC) of MT-BHC SLNs and MT-BHC MPs was 1.4 and 2.5 times that of the BHC solution. Accordingly, the MT-BHC MPs also exhibit the most consistent and long-lasting IOP-lowering effect. Ocular irritation experiments showed no significant toxicity of either. Taken together, MT MPs may have the potential for more effective glaucoma treatment.
