Design and evaluation of novel fast forming pilocarpine-loaded ocular hydrogels for sustained pharmacological response

J Control Release. 2009 Jul 20;137(2):152-9. doi: 10.1016/j.jconrel.2009.03.016. Epub 2009 Mar 31.

Abstract

Fast forming hydrogels prepared by crosslinking a poly(ethylene glycol) (PEG)-based copolymer containing multiple thiol (SH) groups were evaluated for the controlled ocular delivery of pilocarpine and subsequent pupillary constriction. Physical properties of the hydrogels were characterized using UV-Vis spectrophotometry, transmission electron microscopy (TEM), rheometry, and swelling kinetics. Pilocarpine loading efficiency and release properties were measured in simulated tear fluid. The hydrogel formulations exhibited high drug loading efficiency (approximately 74%). Pilocarpine release was found to be biphasic with release half times of approximately 2 and 94 h, respectively, and 85-100% of the drug was released over 8-days. Pilocarpine-loaded (2% w/v) hydrogels were evaluated in a rabbit model and compared to a similar dose of drug in aqueous solution. The hydrogels were retained in the eye for the entire period of the study with no observed irritation. Pilocarpine-loaded hydrogels sustained pupillary constriction for 24 h after administration as compared to 3 h for the solution, an 8-fold increase in the duration of action. A strong correlation between pilocarpine release and pupillary response was observed. In conclusion, the current studies demonstrate that in situ forming PEG hydrogels possess the viscoelastic, retention, and sustained delivery properties required for an efficient ocular drug delivery system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cross-Linking Reagents
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemical synthesis
  • Delayed-Action Preparations / chemistry*
  • Female
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry
  • Microscopy, Electron, Transmission
  • Miotics / administration & dosage*
  • Miotics / chemistry
  • Miotics / pharmacology
  • Pilocarpine / administration & dosage*
  • Pilocarpine / chemistry
  • Pilocarpine / pharmacology
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Pupil / drug effects*
  • Rabbits
  • Rheology
  • Spectrophotometry
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry*
  • Time Factors

Substances

  • Cross-Linking Reagents
  • Delayed-Action Preparations
  • Hydrogels
  • Miotics
  • Sulfhydryl Compounds
  • Pilocarpine
  • Polyethylene Glycols