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

Abstract

Recently, 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.

Graphical Abstract

Keywords:

• Glaucoma therapy
• tear film turnover
• micro-interaction
• montmorillonite
• micro-nanoparticles

Acknowledgments

Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems is acknowledged for their help in performing the experiments.

Disclosure statement

The authors report no conflicts of interest in this work.

Ethical approval statement

New Zealand white rabbits (1.5–2.0 kg) obtained from the Laboratory Animal Center of Southern Medical University, Guangzhou, China (License No: SCXK2020-0050) were fed on standard diets and water at a temperature of 18–25 °C and 60–65% humidity before experiments. All animal experiments which were carried out in New Zealand white rabbits to investigate the safety, efficacy, and pharmacokinetics of formulations were conducted in accordance with the Institutional Animal Care and Use Committee of Guangdong Pharmaceutical University (Acceptance No: gdpulac2020122).

Additional information

Funding

We acknowledge financial support from the National Natural Science Foundation of China (No. 51192052) and the Science and Technology Planning Project of Guangdong Province (No. 2020B1212060055).