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

Eur J Pharm Biopharm. 2016 Dec:109:61-71. doi: 10.1016/j.ejpb.2016.09.010. Epub 2016 Sep 20.

Abstract

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.

Keywords: Carboxymethyl chitosan; Molecular imprinting; Therapeutic contact lenses; Timolol.

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • 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
  • Spectroscopy, Fourier Transform Infrared
  • Staphylococcus aureus / drug effects
  • Tears / metabolism
  • Timolol / administration & dosage*

Substances

  • Anti-Infective Agents
  • Drug Carriers
  • Methacrylates
  • carboxymethyl-chitosan
  • hydroxyethyl methacrylate
  • Timolol
  • Chitosan