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Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries

Paper ID Volume ID Publish Year Pages File Format Full-Text
8250 582 2011 14 PDF Available
Title
Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries
Abstract

Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H2O2 hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (< 1.5%). Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm3) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post-exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal re-epithelialization and wound healing. Histology studies of skin showed that doxycycline loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in an SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries.

Keywords
Disulfide crosslinked hydrogels; Doxycyline; Poly (ethylene glycol); Sustained release
First Page Preview
Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 4, February 2011, Pages 1204–1217
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering