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

• Published in: Drug delivery and translational research Vol. 14; no. 11; pp. 3212 - 3224
• Main Authors: Maulvi, Furqan A., Patel, Ashmi R., Shetty, Kiran H., Desai, Ditixa T., Shah, Dinesh O., Willcox, Mark D. P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2024
• Subjects: Administration, Ophthalmic; Animals; Biomedical and Life Sciences; Biomedicine; Chitosan - administration & dosage; Chitosan - chemistry; Contact Lenses; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Drug Delivery Systems; Drug Liberation; Glaucoma - drug therapy; Intraocular Pressure - drug effects; Muramidase - administration & dosage; Muramidase - chemistry; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Original Article; Pharmaceutical Sciences/Technology; Rabbits; Tears; Timolol - administration & dosage; Timolol - chemistry; Timolol - pharmacokinetics; Glaucoma; Controlled drug delivery; Timolol maleate; Chitosan nanoparticles; Contact lens
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-024-01543-8

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 µg/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. Graphical abstract