4.5 Article

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

期刊

PHARMACEUTICAL RESEARCH
卷 35, 期 2, 页码 -

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SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-017-2298-9

关键词

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

资金

  1. Northern Ireland's Department of Employment and Learning (DEL)
  2. MRC [MC_PC_15035] Funding Source: UKRI

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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 poreforming 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 (chi), increased average molecular weight between crosslinks (Mc) and increased mesh size (epsilon). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were nontoxic 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.

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