Chitosan nanoparticles laden contact lenses for enzyme-triggered controlled delivery of timolol maleate: A promising strategy for managing glaucoma

To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 mu g/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage.