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Emily Dosmar, William F Mieler, Jennifer J Kang Mieler; Controlled vancomycin release from a biodegradable hydrogel ocular drug delivery system. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4145.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to investigate the use of a biodegradable hydrogel to deliver prophylactic vancomycin (VAN) for two weeks following ocular surgery.
VAN was encapsulated in hydrolytically degradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA) and poly(ethylene glycol) diacrylate (PEG-DA) hydrogels. Polymer concentration, polymer PEG-PLLA-DA:PEG-DA ratio, PEG-DA molecular weight (575 MW or 700 MW), and polymerization time were varied to assess the degradation rate and time of hydrogel. Polymer composition was varied to determine swelling ratios. The mesh size of the hydrogel network was estimated using the Flory-Rehner equations. VAN release profiles were conducted at 37°C; at predetermined intervals, samples were analyzed via high-performance liquid chromatography to quantify VAN concentration.
Hydrogel swelling ratios decreased significantly with increased PEG-DA concentrations (p=7×10-4), demonstrating the dependency of hydrogel swelling ratio on polymer concentration. Hydrogel mesh size estimations ranged from 6.79-7.76 nm regardless of investigated polymer composition. Hydrogels degraded slower as polymer concentration increased and hydrogels with a higher degradable to non-degradable polymer ratio showed a faster overall degradation time. Hydrogels with the same polymer ratio degraded more quickly with lower PEG-DA molecular weight: hydrogels rendered with PEG-DA 575MW degraded 5 days faster than those with 700MW. Hydrogels composed of 20:0 PEG-PLLA-DA:PEG-DA exhibited ~30% cumulative release (of theoretically encapsulated VAN) after 24 hours, 40% release by 1 week, and degraded completely in 9 days. Hydrogels with 17:3 PEG-PLLA-DA:PEG-DA showed ~30% release at 24 hours, 33% at 1 week and degraded completely in 16 days.
This study demonstrated that by modifying polymer concentration and ratio, the degradation and release time of VAN can be controlled. Biodegradable hydrogels may have promise for application as prophylactic antibiotic ocular drug delivery devices.
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