Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds.
Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds.
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DOI：
10.1016/j.biomaterials.2009.10.010
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发表时间：
2010-02
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.;DeSantis, Andrea S.;Menjoge, Anupa R.;Hahn, Rita A.;Beloni, John A.;Gordon, Marion K.;Sinko, Patrick J.
关键词：
半芥子气（CEES）和氮芥子气（NM）是化学战剂硫芥子气的常用替代物和起泡剂类似物。在当前的研究中，开发了原位形成的基于聚（乙二醇）（PEG）的多西环素水凝胶，并评价了其在器官培养中CEES和NM暴露的兔角膜中的伤口愈合功效。通过紫外-可见分光光度计、流变仪和溶胀动力学对水凝胶进行表征，表明水凝胶是光学透明的，具有良好的机械强度和相对低的溶胀度（<7%）。发现从水凝胶盘（0.25%w/v）的体外多西环素释放是双相的，释放半衰期分别为约12和72小时，在7天的时间内释放80-100%。发现多西环素通过起泡的受伤角膜的渗透比非受伤角膜高2.5至3.4倍。组织学和免疫荧光研究显示，与在磷酸盐缓冲盐水（PBS，pH 7.4）中递送的类似剂量的多西环素相比，多西环素水凝胶显著降低了基质金属蛋白酶-9（MMP-9），并改善了暴露于起泡剂的角膜的愈合。总之，目前的研究表明，多西环素-PEG水凝胶加速了水疱性损伤后的角膜伤口愈合，为眼部芥子气损伤提供了一种治疗选择。
Half mustard (CEES) and nitrogen mustard (NM) are commonly used surrogates and vesicant analogs of the chemical warfare agent sulfur mustard. In the current study, in situ forming poly(ethylene glycol) (PEG)-based doxycycline hydrogels are developed and evaluated for their wound healing efficacy in CEES and NM exposed rabbit corneas in organ culture. The hydrogels, characterized by UV-Vis spectrophotometry, rheometry, and swelling kinetics, showed that the hydrogels are optically transparent, have good mechanical strength and a relatively low degree of swelling (<7%). In vitro doxycycline release from the hydrogel disks (0.25% w/v) was found to be biphasic with release half times of ~12 and 72 h, respectively, with 80–100% released over a 7-day period. Permeation of doxycycline through vesicant wounded corneas was found to be 2.5 to 3.4 fold higher than non-wounded corneas. Histology and immunofluorescence studies showed a significant reduction of matrix metalloproteinase-9 (MMP-9) and improved healing of vesicant exposed corneas by doxycycline hydrogels compared to a similar dose of doxycycline delivered in phosphate buffered saline (PBS, pH 7.4). In conclusion, the current studies demonstrate that the doxycycline-PEG hydrogels accelerate corneal wound healing after vesicant injury offering a therapeutic option for ocular mustard injuries.
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