Extended wear therapeutic contact lens fabricated from timolol imprinted carboxymethyl chitosan-g-hydroxy ethyl methacrylate-g-poly acrylamide as a onetime medication for glaucoma

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 109; pp. 61 - 71
• Main Authors: Anirudhan, T.S., Nair, Anoop S., Parvathy, J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2016
• Subjects: Animals; Anti-Infective Agents - chemistry; Carboxymethyl chitosan; Cell Line; Cell Survival; Chitosan - analogs & derivatives; Chitosan - chemistry; Contact Lenses; Disease Models, Animal; Drug Carriers - chemistry; Drug Delivery Systems; Elastic Modulus; Escherichia coli - drug effects; Glaucoma - drug therapy; Humans; Kinetics; Methacrylates - chemistry; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Molecular imprinting; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus - drug effects; Tears - metabolism; Therapeutic contact lenses; Timolol; Timolol - administration & dosage; DPPH; Carboxymethyl chitosan; AAm; pHEMA; CmCS-g-HEMA-g-pAAm; CS; HEMA; TML; TCL 1C, 2C, 3C and 4C; NIP; MIP; XTT; CmCS; TCL; Molecular imprinting; Timolol; Therapeutic contact lenses
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2016.09.010

A novel timolol maleate imprinted carboxymethyl chitosan-grafted-hydroxy ethyl methacrylate-grafted-polyacrylamide was embedded onto poly HEMA matrix for improved drug release efficacy and reusable therapeutic contact lens.
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•A novel molecularly imprinted polymer capable of sustained release of timolol was successfully synthesized and characterized.•The fabricated contact lens could rebind with drug molecule for a tentative four cycles by simple soaking procedure.•Mechanical and optical properties of the contact lens were maintained for all four cycles.•The prepared contact lens serves as an economical way for onetime glaucoma medication.
An extended wear therapeutic contact lens (TCL) for the sustained delivery of timolol maleate (TML) was fabricated based on molecular imprinting technique. The designed TCL comprised of a TML imprinted copolymer of carboxymethyl chitosan-g-hydroxy ethyl methacrylate-g-polyacrylamide (CmCS-g-HEMA-g-pAAm) embedded onto a poly HEMA matrix (pHEMA). Successful reloading of TML onto the lens was monitored using a simple and novel UV–Visible spectrophotometric method which showed an excellent reloading capacity of 6.53μgTML/TCL. The in vitro drug release profile in lacrimal fluid after each cycle was fitted onto Higuchi model of drug release suggesting diffusion release mechanism with no polymer degradation. Also, the TML release kinetics indicated a sustained drug delivery which can effectively achieve the therapeutic index of TML leading to a onetime medication for glaucoma. Biological activity of eluted drug after each cycle and cell viability of the TCL were verified using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,3-bis(2-methoxynitro-5-sulfophenyl)-5-(phenylaminocarbonyl)-2H-tetrazolium hydroxide (XTT) assay, respectively.