Antibacterial layer-by-layer coatings to control drug release from soft contact lenses material

Int J Pharm. 2018 Dec 20;553(1-2):186-200. doi: 10.1016/j.ijpharm.2018.10.041. Epub 2018 Oct 17.

Abstract

In this study we investigated the possibility of using polyelectrolytes with antibacterial properties to form layer-by-layer (LbL) coatings on contact lens materials with the objective of controlling the release of ophthalmic drugs, while minimizing bacterial growth. A silicone-based hydrogel recently proposed by our group was chosen as a drug releasing soft contact lens (SCL) material and three drugs were tested: moxifloxacin hydrochloride (MXF), chlorhexidine diacetate monohydrate (CHX), and diclofenac sodium salt (DIC). Employed coatings involved combinations of sodium alginate (ALG), chitosan (CHI), sodium hyaluronate (HA) and polylysine hydrobromide (PLL), using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as a cross-linking agent. Controlled release of DIC was achieved using two double layers of the following combinations: ALG/PLL (EDC), HA (EDC)/CHI and HA/PLL (EDC) + Drug. Furthermore, the physical properties of the coated lens material were kept, or even improved, and bacterial growth was reduced. In contrast, these coatings did not retard the release of MXF and CHX. The specificity of the barrier effect of these LbL films for DIC may be attributed to the formation of reversible interactions between DIC and the polyelectrolyte chains. A top layer of HA was needed to reduce the interaction with tear proteins. The in vivo efficacy of a contact lens coated with ALG/PLL (EDC)//HA and loaded with DIC was predicted using a simplified mathematical model to estimate the drug concentration in the tear fluid. The period of time during which the estimated concentration of DIC remained above the half-maximum inhibitory concentrations for the active enzymes in the process of inflammation, was at least double that obtained with the uncoated sample.

Keywords: Antibacterial properties; Controlled drug release; Layer-by-layer coatings; Ophthalmic drugs; Soft contact lenses.

MeSH terms

  • Administration, Ophthalmic
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Chemistry, Pharmaceutical / methods
  • Chlorhexidine / administration & dosage
  • Contact Lenses, Hydrophilic*
  • Cross-Linking Reagents / chemistry
  • Delayed-Action Preparations
  • Diclofenac / administration & dosage
  • Drug Liberation
  • Excipients / chemistry
  • Models, Theoretical*
  • Moxifloxacin / administration & dosage
  • Polyelectrolytes / chemistry
  • Polyelectrolytes / pharmacology*
  • Tears / metabolism

Substances

  • Anti-Bacterial Agents
  • Cross-Linking Reagents
  • Delayed-Action Preparations
  • Excipients
  • Polyelectrolytes
  • Diclofenac
  • Chlorhexidine
  • Moxifloxacin