Comparative study of nanosized cross-linked sodium-, linear sodium- and zinc-hyaluronate as potential ocular mucoadhesive drug delivery systems

Int J Pharm. 2015 Oct 15;494(1):321-8. doi: 10.1016/j.ijpharm.2015.08.024. Epub 2015 Aug 28.

Abstract

Hyaluronic acid (HA) and its derivatives play important roles in many fields of therapy, such as arthritis treatment, plastic surgery, dermatology, otology, ophthalmology, etc. With a view to increase the beneficial properties of HA in ocular drug delivery, many types of chemical structural modifications have been performed. In the course of our research work, we characterized nanosized cross-linked - (CLNaHA), linear sodium hyaluronate (NaHA) and zinc-hyaluronate (ZnHA), as potential ocular drug delivery systems. The aim was to determine the influence of the structure on biocompatibility, mucoadhesion and drug release. The structure was characterized by means of rheology. The cytotoxicity of the samples was determined on rabbit corneal epithelial cells (RCE) by the MTT test. Mucoadhesion measurements were made by a rheological method in vitro and by tensile tests in vitro and ex vivo. The release of sodium diclofenac, a frequently used non-steroidal anti-inflammatory drug with low bioavailability, from the gels was determined with a vertical Franz diffusion cell. The results demonstrated that all three derivatives have adequate mucoadhesive properties and their rapid drug release profiles are beneficial in ocular therapy. Thanks to these properties, the bioavailability of the ophthalmic preparations can be increased, especially with the application of CLNaHA.

Keywords: Cross-linked sodium hyaluronate; Cytotoxicity; Hyaluronic acid; Mucoadhesion; Ocular drug release; Zinc hyaluronate.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesives / adverse effects
  • Adhesives / chemistry*
  • Animals
  • Biocompatible Materials / adverse effects
  • Biocompatible Materials / chemistry
  • Biological Availability
  • Cell Survival / drug effects
  • Diclofenac / chemistry
  • Diclofenac / pharmacokinetics
  • Drug Delivery Systems / adverse effects
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Epithelium, Corneal / drug effects
  • Gels / adverse effects
  • Gels / chemistry*
  • Hyaluronic Acid / adverse effects
  • Hyaluronic Acid / chemistry*
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / chemistry*
  • Rabbits
  • Rheology

Substances

  • Adhesives
  • Biocompatible Materials
  • Gels
  • Organometallic Compounds
  • zinc hyaluronate complex
  • Diclofenac
  • Hyaluronic Acid