Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair.
Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair.
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DOI：
10.1016/j.jconrel.2012.05.034
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发表时间：
2012-08-10
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Downing TL;Wang A;Yan ZQ;Nout Y;Lee AL;Beattie MS;Bresnahan JC;Farmer DL;Li S
脊髓损伤（SCI）仍然是再生医学面临的主要挑战。SCI后，轴突生长抑制剂和其他炎症反应阻止功能恢复。以前的研究已经证明，咯利普兰，抗炎和环磷酸腺苷保留小分子，改善脊髓再生时，提供全身。然而，最近的研究表明，咯利普兰在脊髓修复中有一些不良影响。在这里，我们开发了一种药物输送平台，用于将咯利普兰局部输送到脊髓中。在体外表征了药物洗脱微纤维贴片用于连续递送高剂量和低剂量咯利普兰浓度的潜力。在C5半切后，用装有低剂量和高剂量咯利普兰的贴片治疗无胸腺大鼠。一般而言，用低剂量咯利普兰处理的动物相对于所有其他组经历了更大的功能和解剖学恢复。高剂量咯利普兰治疗的结果与未治疗的结果相似。此外，高剂量给药动物的存活率降低，表明达到了全身毒性。由于能够控制药物剂量在脊髓内的局部释放，药物洗脱微纤维贴片证明了咯利普兰适当的局部释放动力学的重要性，证明了它们作为研究和修复SCI的治疗平台的有用性。
Spinal cord injury (SCI) remains a major challenge for regenerative medicine. Following SCI, axon growth inhibitors and other inflammatory responses prevent functional recovery. Previous studies have demonstrated that rolipram, an anti-inflammatory and cyclic adenosine monophosphate preserving small molecule, improves spinal cord regeneration when delivered systemically. However, more recent studies showed that rolipram has some adverse effects in spinal cord repair. Here, we developed a drug-delivery platform for the local delivery of rolipram into the spinal cord. The potential of drug-eluting microfibrous patches for continuous delivery of high and low-dose rolipram concentrations was characterized in vitro. Following C5 hemisections, athymic rats were treated with patches loaded with low and high doses of rolipram. In general, animals treated with low-dose rolipram experienced greater functional and anatomical recovery relative to all other groups. Outcomes from the high-dose rolipram treatment were similar to those with no treatment. In addition, high-dose treated animals experienced reduced survival rates suggesting that systemic toxicity was reached. With the ability to control the release of drug dosage locally within the spinal cord, drug-eluting microfibrous patches demonstrate the importance of appropriate local release-kinetics of rolipram, proving their usefulness as a therapeutic platform for the study and repair of SCI.
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影响因子：
5.3
作者：
Sharp, Kelli G.;Flanagan, Lisa A.;Yee, Kelly Matsudaira;Steward, Oswald
通讯作者：
Steward, Oswald
DOI：
10.1073/pnas.0704581104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Hashi, Craig K.;Zhu, Yiqian;Li, Song
通讯作者：
Li, Song
DOI：
10.1073/pnas.052678899
发表时间：
2002-03-05
影响因子：
11.1
作者：
Teng, YD;Lavik, EB;Snyder, EY
通讯作者：
Snyder, EY
影响因子：
5.3
作者：
Koopmans, Guido C.;Deumens, Ronald;Brook, Gary A.
通讯作者：
Brook, Gary A.
影响因子：
5.3
作者：
Niederöst, BP;Zimmermann, DR;Bandtlow, CE
通讯作者：
Bandtlow, CE