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3D-Wound healing model: Influence of morphine and solid lipid nanoparticles

机译:3D伤口愈合模型:吗啡和固体脂质纳米颗粒的影响

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For efficient pain reduction in severe skin wounds, topically applied opioids may be a new option. Moreover, by stimulating keratinocyte migration opioids may also accelerate wound healing. Yet, conventional formulations failed to consistently provide sufficient pain control in patients which may be due to local drug degradation or insufficient concentrations at the target site. After having excluded major morphine glucuronidation by keratinocytes and fibroblasts, we next aimed for an optimised formulation. Since long intervals for painful wound dressing changes are intended, the formulations should allow for prolonged opioid release and should not impair the healing process. We developed morphine-loaded solid lipid nanoparticles (SLN, mean size about 180 nm), and tested improvement of wound closure in a new human-based 3D-wound healing model. Standardised wounds were induced by CO2-laser irradiation of reconstructed human full-thickness skin equivalents (EpiDermET (TM)). Morphine, morphine-loaded and unloaded SLN accelerated reepithelialization. Keratinocytes almost completely covered the dermis equivalent after 4 days, which was not the case when applying the vehicle. In conclusion, acceleration of wound closure, low cytotoxicity and irritation as well as possible prolonged morphine release make SLN an interesting approach for innovative wound management
机译:为了有效减轻严重皮肤伤口的疼痛,局部应用阿片类药物可能是一个新的选择。此外,通过刺激角质形成细胞迁移,阿片类药物也可以加速伤口愈合。但是,常规制剂不能始终如一地在患者中提供足够的疼痛控制,这可能是由于局部药物降解或靶部位浓度不足所致。在排除了角质形成细胞和成纤维细胞对主要的吗啡葡萄糖醛酸化作用后,我们接下来的目标是优化配方。由于需要长时间间隔进行痛苦的伤口敷料更换,因此该制剂应允许阿片类药物长时间释放,并且不应损害愈合过程。我们开发了加载吗啡的固体脂质纳米颗粒(SLN,平均粒径约180 nm),并在基于人的新3D伤口愈合模型中测试了伤口闭合的改善。通过CO2激光辐照重建的人类全层皮肤等效物(EpiDermET(TM))诱导标准化伤口。吗啡,吗啡装载和卸载的SLN加速了再上皮形成。 4天后,角质形成细胞几乎完全覆盖了真皮等价物,而施用媒介物则不是这种情况。总之,伤口闭合的加速,低细胞毒性和刺激性以及可能的吗啡释放可能延长,使SLN成为创新伤口处理的有趣方法

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