Department of Pharmacology, Sechenov University, 119019 Moscow, Russia.
Department of Pharmacology, University Technology MARA, Kuala Lumpur 50450, Malaysia.
Molecules. 2022 May 30;27(11):3507. doi: 10.3390/molecules27113507.
The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.
成人中最常见的原发性恶性脑肿瘤是神经胶质瘤。胶质母细胞瘤是最常见和侵袭性最强的神经胶质瘤肿瘤亚型。目前胶质母细胞瘤的治疗标准包括手术、放疗和药物治疗方法的结合。药物治疗目前包括替莫唑胺（TMZ），一种烷化剂，和贝伐单抗，一种重组单克隆 IgG1 抗体，它选择性地结合并抑制血管内皮生长因子的生物学活性。在胶质母细胞瘤放疗中加入 TMZ 可将患者的存活时间从 12.1 个月延长至 14.6 个月。TMZ 对脑肿瘤的特异性在很大程度上取决于其药代动力学的特殊方面。TMZ 是一种口服生物利用前药，在胃肠道中被很好地吸收，在不需要肝脏参与的生理条件下自发转化为其活性烷化代谢物 5-(3-甲基三嗪-1-基)咪唑-4-甲酰胺（MTIC）。在血浆中产生的 MTIC 不能穿过 BBB，而是在大脑中局部形成。一种提高 TMZ 化疗治疗胶质母细胞瘤效果的有前途的方法是防止其在外周组织中水解，从而增加脑内药物浓度，纳米输送系统可以提供这种浓度。该综述讨论了使用纳米载体提高 TMZ 疗效的可能途径。
