Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries.
Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries.
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DOI：
10.1016/j.biomaterials.2010.08.117
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发表时间：
2011-02
期刊：
影响因子：
14
通讯作者：
Sinko, Patrick J.
中科院分区：
文献类型：
--
作者：
Anumolu, SivaNaga S.;Menjoge, Anupa R.;Deshmukh, Manjeet;Gerecke, Donald;Stein, Stanley;Laskin, Jeffrey;Sinko, Patrick J.
多西环素水凝胶含有可逆的二硫键交联物，用于皮肤伤口愈合。用氮芥末(NM)作为替代物来模拟化学战剂硫芥末的发泡作用。以过氧化氢(H_2O_2水凝胶)或8-臂-S-硫代吡啶(S-TP水凝胶)为交联剂，将含有多个硫醇(-SH)基团的8-臂聚乙二醇缩乙二醇(-SH)聚合物原位交联成水凝胶。配方添加剂(甘油、PVP和PEG600)被发现可以促进真皮水凝胶保持长达24小时。水凝胶表现出高机械强度和低膨胀度(<；1.5%)。多西环素从水凝胶中的释放是两相的，在体外可持续10天。强的环素(8.5 mg/cm~3)暴露后24、72和168 h皮肤通透性均高于未用发泡剂的对照组，其中72 h达高峰，168 h的降低与表皮再上皮化和创面愈合有关。皮肤组织学研究表明，在SKH-1小鼠模型中，与未经处理的皮肤和使用安慰剂水凝胶处理的皮肤相比，加载多西环素(0.25%w/v)的水凝胶可改善暴露在NM的皮肤上的伤口愈合反应。综上所述，基于聚乙二醇基的多西环素水凝胶在芥子气损伤的皮肤创面修复中具有广阔的应用前景。
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 reepithelialization 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 a SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries.
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影响因子：
14
作者：
Gupta, D;Tator, CH;Shoichet, MS
通讯作者：
Shoichet, MS
DOI：
10.1007/s10856-008-3627-7
发表时间：
2009-02-01
影响因子：
3.7
作者：
Costa, Ezequiel de Souza, Jr.;Pereira, Marivalda M.;Mansur, Herman S.
通讯作者：
Mansur, Herman S.
影响因子：
14
作者：
Anumolu, SivaNaga S.;DeSantis, Andrea S.;Menjoge, Anupa R.;Hahn, Rita A.;Beloni, John A.;Gordon, Marion K.;Sinko, Patrick J.
通讯作者：
Sinko, Patrick J.
影响因子：
4.9
作者：
Milano, S;Arcoleo, F;Cillari, E
通讯作者：
Cillari, E
影响因子：
5.8
作者：
Ferrero, C;Muñoz-Ruiz, A;Jiménez-Castellanos, MR
通讯作者：
Jiménez-Castellanos, MR