Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery

Pharm Res. 2018 Jan 16;35(2):36. doi: 10.1007/s11095-017-2298-9.

Abstract

Purpose: To investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents.

Methods: Triamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin.

Results: Regardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period.

Conclusion: Photocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.

Keywords: ocular drug delivery; photocrosslinked; poly(ethylene glycol) diacrylate; protein delivery; triamcinolone acetonide.

MeSH terms

  • Administration, Ophthalmic
  • Biological Products / administration & dosage
  • Biological Products / pharmacokinetics*
  • Cell Line
  • Diabetic Retinopathy / drug therapy
  • Drug Compounding / methods
  • Drug Delivery Systems / methods*
  • Drug Implants
  • Drug Liberation*
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacokinetics*
  • Humans
  • Macular Degeneration / drug therapy
  • Materials Testing
  • Molecular Weight
  • Ovalbumin / administration & dosage
  • Ovalbumin / pharmacokinetics
  • Polyethylene Glycols / chemical synthesis*
  • Porosity
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / drug effects
  • Triamcinolone Acetonide / administration & dosage
  • Triamcinolone Acetonide / pharmacokinetics

Substances

  • Biological Products
  • Drug Implants
  • Glucocorticoids
  • poly(ethylene glycol)diacrylate
  • Polyethylene Glycols
  • Ovalbumin
  • Triamcinolone Acetonide