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J Control Release:外泌体作为药物载体治疗帕金森疾病

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外泌体作为一种自然生物形成的纳米级膜泡在过去的几年里受到了人们相当大的关注。外泌体具有磷脂双分子层结构,膜上具有很多蛋白成分,可与细胞膜相互作用。University of North Carolina, Chapel Hill的研究者们提出假设:单核细胞和巨噬细胞分泌的外泌体可避免单核巨噬细胞的吞噬,同时增强其携带的药物的传递进而提高药物治疗的效果。在这个假设下,他们成功地为抗氧化剂、过氧化氢酶,开发了一个新的基于外泌体的药物传递系统来治疗帕金森疾病。使用不同的方法将过氧化氢酶在体外载入外泌体:室温孵育、皂素透化、反复冻融、超声或者挤压。获得的含过氧化氢酶的外泌体(exoCAT)大小约为100-200nm。利用超声和挤压、或皂素透化对外泌体的改善后可提高药物载入的效率、维持药物的持续释放、和防止过氧化氢酶被蛋白酶降解。外泌体可在体外呗神经细胞获取。在鼻腔给药后在小鼠的大脑中检测到了大量的外泌体。含过氧化氢酶的外泌体(exoCAT)在体外和体内帕金森模型上都具有显著的神经保护的作用。总的来说,基于外泌体的过氧化氢酶给药方式为治疗免疫和神经退行性疾病提供了多种可能性。

1-s2.0-S0168365915X00083-cov150h

原文来源:Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., . . . Batrakova, E. V. (2015). Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release. doi: 10.1016/j.jconrel.2015.03.033

Abstract: Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze–thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100–200 nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.

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外泌体资讯网 J Control Release:外泌体作为药物载体治疗帕金森疾病

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