Evaluation of an injectable thermosensitive hydrogel as drug delivery implant for ocular glaucoma surgery

PLoS One. 2014 Jun 20;9(6):e100632. doi: 10.1371/journal.pone.0100632. eCollection 2014.

Abstract

In this study, a biodegradable thermo-sensitive hydrogel from poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (PTMC15-F127-PTMC15) was designed and evaluated as an injectable implant during ocular glaucoma filtration surgery in vivo and in vitro. Mitomycin C (MMC) was loaded into this hydrogel for controlled released to prolong the efficacy and to reduce the long-term toxicity. The properties of the hydrogel were confirmed using 1H NMR and gel permeation chromatography (GPC). Compared to the Pluronic F127 hydrogel, the PTMC15-F127-PTMC15 hydrogel showed a good solution-gel transition temperature at 37°C, a lower work concentration of 5% w/v and a longer mass loss time of more than 2 weeks. The in vitro study showed that the drug could be released from PTMC15-F127-PTMC15 (5% w/v) hydrogel for up to 16 days with only 57% of drug released in the first day. Moreover, the cell toxicity, which was tested via LDH and ANNEXIN V/PI, decreased within 72 h in human tenon's fibroblast cells (HTFs). The in vivo behavior in a rabbit glaucoma filtration surgery model indicated that this hydrogel loaded with 0.1 mg/ml MMC led to a better functional bleb with a prolonged mean bleb survival time (25.5±2.9 days). The scar tissue formation, new collagen deposition and myofibroblast generation appeared to be reduced upon histological and immunohistochemistry examinations, with no obvious side effects and inflammatory reactions. The in vitro and in vivo results demonstrated that this novel hydrogel is a safe and effective drug delivery candidate in ocular glaucoma surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biocompatible Materials / administration & dosage
  • Drug Delivery Systems*
  • Drug Implants
  • Filtering Surgery / methods*
  • Glaucoma / drug therapy
  • Glaucoma / pathology
  • Glaucoma / surgery*
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / administration & dosage*
  • Mitomycin / administration & dosage
  • Rabbits

Substances

  • Biocompatible Materials
  • Drug Implants
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Mitomycin

Grants and funding

This work was supported by the China National Natural Science Foundation (NO. 81170846 and U1134007), the Fundamental Research Funds of State Key Laboratory of Ophthalmology of China (N0. 2012PI02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.