Cross-linked hyaluronan films loaded with acetazolamide-cyclodextrin-triethanolamine complexes for glaucoma treatment

Ther Deliv. 2018 Feb 1;9(3):205-220. doi: 10.4155/tde-2017-0087.

Abstract

Aim: This work aimed to design and characterize cross-linked hyaluronic acid-itaconic acid films loaded with acetazolamide-hydroxypropyl β cyclodextrin-triethanolamine complexes.

Materials & methods: Films were cross-linked with itaconic acid and poly(ethyleneglycol)-diglycidylether. Biopharmaceutical properties were assessed by evaluating in vitro drug release rate, biocompatibility in a human corneal epithelial cell line, bioadhesiveness with pig gastric mucin, in vivo bioadhesion and efficacy.

Results: Showed good mechanical properties and oxygen permeability. Proliferation rate of corneal cells was affected by highest acetazolamide concentration. Bioadhesive interaction exhibited a water movement from pig mucin to the film; in vivo experiments showed strong bioadhesion for 8 h and hypotensive effect for almost 20 h.

Conclusion: Experimental set showed promising performance and encouraged future studies to optimize formulation. [Formula: see text].

Keywords: acetazolamide; cyclodextrin inclusion complex; glaucoma; hyaluronan; topical.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / administration & dosage*
  • 2-Hydroxypropyl-beta-cyclodextrin / pharmacokinetics
  • Acetazolamide / administration & dosage*
  • Acetazolamide / pharmacokinetics
  • Administration, Ophthalmic
  • Animals
  • Cell Line
  • Cross-Linking Reagents / chemistry
  • Drug Combinations
  • Drug Liberation
  • Epithelial Cells
  • Ethanolamines / administration & dosage*
  • Ethanolamines / pharmacokinetics
  • Glaucoma / drug therapy*
  • Humans
  • Hyaluronic Acid / chemistry*
  • Male
  • Models, Animal
  • Rabbits

Substances

  • Cross-Linking Reagents
  • Drug Combinations
  • Ethanolamines
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Hyaluronic Acid
  • triethanolamine
  • Acetazolamide