University of the Witwatersrand, Department of Pharmacy and Pharmacology, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
Expert Opin Drug Deliv. 2010 Feb;7(2):203-24. doi: 10.1517/17425240903483166.
Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors.
Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated.
The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated.
This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the effective management of PD.
尽管帕金森病（PD）在近 200 年前被发现，但它的治疗和管理仍然是巨大的挑战，因为多巴胺能黑质神经元进行性丧失，随着疾病的进展，患者经历运动并发症以及药物治疗管理的缺点仍然存在。在 PD 的管理中，已经使用了各种治疗剂，包括左旋多巴（l-DOPA）、司来吉兰、金刚烷胺、溴隐亭、恩他卡朋、盐酸普拉克索和最近的依他司琼和雷沙吉兰。在所有的药物中，虽然 l-DOPA 是最古老的，但仍然是最有效的。l-DOPA 更容易给药，耐受性更好，更便宜，几乎所有 PD 患者都需要它。然而，由于代谢作用，随后的生物利用度低以及其血浆水平的不规则波动，l-DOPA 在晚期 PD 中的疗效显著降低。为了提高 l-DOPA 的生物利用度并减少其血浆波动以及据称源自纹状体多巴胺受体脉冲刺激的患者的运动并发症，已经取得了重大进展，以改善 l-DOPA 的传递。
用于 l-DOPA 传递的药物传递系统包括速释制剂、液体制剂、分散片、控释制剂、双重释放制剂、微球、输注和透皮传递等。在这篇综述中，详细阐述了过去三十年中开发的 l-DOPA 负载药物传递系统。
最终目的是批判性地评估迄今为止为改善 l-DOPA 吸收、生物利用度和维持恒定的血浆浓度而做出的尝试，包括涉及的药物传递技术。
这篇综述强调了神经药物学处于悬崖边缘的事实，预计这将促使研究人员迈出那一步，为有效管理 PD 生成创新的传递系统。
