UC Berkeley & UCSF Joint Graduate Program in Bioengineering, Berkeley/San Francisco, CA, USA.
J Control Release. 2012 Aug 10;161(3):910-7. doi: 10.1016/j.jconrel.2012.05.034. Epub 2012 May 23.
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.
脊髓损伤 (SCI) 仍然是再生医学的一大挑战。SCI 后,轴突生长抑制剂和其他炎症反应阻止了功能恢复。先前的研究表明,罗利普兰是一种抗炎和环磷酸腺苷保护的小分子,当全身给药时,可改善脊髓再生。然而,最近的研究表明,罗利普兰在脊髓修复中有一些不良反应。在这里,我们开发了一种用于将罗利普兰局部递送到脊髓的药物输送平台。体外研究了载药微纤维贴片持续输送高剂量和低剂量罗利普兰的潜力。在 C5 半切术后,对载有低剂量和高剂量罗利普兰的贴片进行了无胸腺大鼠的治疗。一般来说,与其他所有组相比,低剂量罗利普兰治疗的动物经历了更大的功能和解剖学恢复。高剂量罗利普兰治疗的结果与无治疗的结果相似。此外,高剂量治疗的动物存活率降低,表明已达到全身毒性。通过能够在脊髓内局部控制药物剂量的释放,载药微纤维贴片证明了罗利普兰适当的局部释放动力学的重要性,证明了它们作为 SCI 研究和修复的治疗平台的有用性。