Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles

Macromol Biosci. 2018 Jan;18(1). doi: 10.1002/mabi.201700200. Epub 2017 Aug 23.

Abstract

Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures.

Keywords: drug delivery vehicle; hyaluronic acid; poly(glyceryl glycerol); polymer-from-polymer release; vitreous.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Glycerol / chemistry
  • Glycerol / pharmacology
  • Glyceryl Ethers / chemistry
  • Glyceryl Ethers / pharmacology
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Intravitreal Injections
  • Kinetics
  • Molecular Weight
  • Polymers / chemistry*
  • Polymers / pharmacology
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / pathology
  • Vitreous Body / drug effects
  • Water / chemistry

Substances

  • Drug Carriers
  • Glyceryl Ethers
  • Polymers
  • Water
  • Hyaluronic Acid
  • Glycerol