Mazibuko Zamanzima, Choonara Yahya E, Kumar Pradeep, Du Toit Lisa C, Modi Girish, Naidoo Dinesh, Pillay Viness
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
J Pharm Sci. 2015 Apr;104(4):1213-29. doi: 10.1002/jps.24322. Epub 2015 Jan 5.
Amyotrophic lateral sclerosis (ALS) has a multitude of factors implicated in its etiology. The complex neuro-etiology and the restrictive nature of the blood-brain barrier (BBB) have significantly hindered the drug therapy of ALS. Riluzole, a moderately performing drug, is the only agent approved for treating ALS. However, several promising nanocarrier approaches are surfacing that can provide more efficient drug delivery. In addition, biologicals such as stem cells are able to carry neurotrophic factors to their target site, providing motor neurons with the benefits of both, stem cells and neurotrophic factors. This review examines the current drug delivery strategies investigated for optimally treating ALS and related neurodegenerative disorders. Examples include cerium oxide nanoparticles in Alzheimer's disease, odorranalectin, and lactoferrin-coupled PEG-PLGA nanoparticles for urocortin transportation in Parkinson's disease that can also be employed in ALS to bypass the BBB and increase drug bioavailability. A concise incursion into the progress (and lack thereof) made in ALS clinical trials is also discussed. Nanocarriers can potentially eliminate the challenges of poor drug bioavailability in ALS as they have been proven to cross the BBB and reach target sites while minimizing systemic side-effects. Nanocarrier-based delivery of ALS drugs is an area that requires much needed investigation.
肌萎缩侧索硬化症(ALS)的病因涉及多种因素。复杂的神经病因以及血脑屏障(BBB)的限制性本质严重阻碍了ALS的药物治疗。利鲁唑是一种疗效一般的药物,是唯一被批准用于治疗ALS的药物。然而,一些有前景的纳米载体方法正在出现,它们能够提供更有效的药物递送。此外,诸如干细胞等生物制剂能够将神经营养因子携带至其靶位点,为运动神经元提供干细胞和神经营养因子两者的益处。本综述考察了目前为最佳治疗ALS及相关神经退行性疾病而研究的药物递送策略。实例包括用于阿尔茨海默病的氧化铈纳米颗粒、嗅沟蛙皮素,以及用于帕金森病中促肾上腺皮质激素释放激素转运的乳铁蛋白偶联聚乙二醇-聚乳酸-羟基乙酸共聚物纳米颗粒,这些也可用于ALS以绕过血脑屏障并提高药物生物利用度。还讨论了ALS临床试验中取得的进展(以及未取得进展的情况)。纳米载体有可能消除ALS中药物生物利用度差的挑战,因为它们已被证明能够穿过血脑屏障并到达靶位点,同时将全身副作用降至最低。基于纳米载体的ALS药物递送是一个急需研究的领域。