a Department of Nanotechnology , Graduate University of Advanced Technology , Kerman , Iran.
b Chemistry Department , University of Payam-Noor , Tehran , Iran.
Artif Cells Nanomed Biotechnol. 2018;46(sup1):434-446. doi: 10.1080/21691401.2018.1430583. Epub 2018 Jan 29.
Loss of dopamine-secreting neurons in the midbrain causes Parkinson's disease. L-DOPA, the precursor to the neurotransmitters dopamine, crosses vast majority of physiological and biochemical barriers that dopamine cannot. But most levodopa is decarboxylated to dopamine before it reaches the brain. This causes to little therapeutic gain with strong peripheral side effects. Benserazide is an irreversible inhibitor of peripheral aromatic L-amino acid decarboxylase that prevents the breakdown of levodopa in the bloodstream. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of Levodopa drug. Biocompatible nano-sized drug carriers could address these challenges at molecular level. Thus calculations of drug loading ability of acid-functionalized CNT for the benserazide as a nanodug carrier complex for L-DOPA were performed. In this regard, evaluation of all adsorption features of the most stable conformer of benserazide molecule onto carboxylated carbon nanotube is critical. To determine the minimum energy conformer of benserazide, the molecular structure and conformational analysis of 512 possible conformers have been subjected to first principle quantum mechanical calculations. Our work established a novel and easy-to-make formulation of benserazide/carboxylated CNT conjugate with extremely high drug loading efficiency of Levodopa for Parkinson disease treatment.
中脑多巴胺能神经元的丧失导致帕金森病。左旋多巴（多巴胺的前体）可穿过大多数多巴胺无法穿过的生理和生化屏障。但大多数左旋多巴在到达大脑之前就被脱羧转化为多巴胺。这导致治疗效果不佳，同时伴有强烈的外周副作用。卡比多巴是一种不可逆的外周芳香族 L-氨基酸脱羧酶抑制剂，可防止左旋多巴在血液中分解。挑战在于提高左旋多巴药物的治疗效率、生物利用度和降低不良反应。生物相容性的纳米级药物载体可以在分子水平上解决这些挑战。因此，对酸功能化 CNT 对作为 L-DOPA 纳米药物载体复合物的卡比多巴的药物负载能力进行了计算。在这方面，评估苯扎那肽分子最稳定构象吸附到羧化碳纳米管上的所有吸附特征至关重要。为了确定苯扎那肽的最低能量构象，对 512 种可能构象的分子结构和构象分析进行了第一性原理量子力学计算。我们的工作建立了一种新的、易于制备的卡比多巴/羧化 CNT 缀合物配方，具有极高的左旋多巴药物负载效率，可用于帕金森病的治疗。
