不同给药途径的治疗性纳米抗体研究进展

骆驼科及鲨鱼科动物血清中天然存在的纳米抗体具有不同于传统单克隆抗体的独特结构和分子量,这为抗体药物开发提供了全新的思路。纳米抗体较小的分子量和优异的稳定性使其在给药方面具有更大的灵活性,可以在一定程度上克服传统单克隆抗体在给药途径方面存在的局限性。同时,较小的分子量使纳米抗体具有双重药代动力学特征,既有优异的组织渗透性,又表现出快速的血液清除。重点介绍纳米抗体的药物代谢动力学特征和进一步改善药代动力学的方法,综述不同给药途径的纳米抗体药物研究进展,对其治疗特定疾病的可行性、安全性以及治疗效果进行分析,以期为纳米抗体药物研发中给药途径的选择提供参考。

Research Progress of Therapeutic Nanobodies with Different Routes of Administration

The nanobodies naturally existing in the sera of camels and Sharks provide a new idea for the development of antibody drugs because of their unique structural characteristics and molecular weight different from traditional monoclonal antibodies. In particular, the small molecular weight and excellent stability of nanobodies enable them to have greater flexibility in drug delivery. They can withstand harsh biophysical environments and are developed into oral preparations and aerosolized inhalants, which to some extent solves the challenges and limitations of traditional monoclonal antibodies in drug delivery routes. However, the small molecular weight also makes the nanobody have dual pharmacokinetic characteristics after administration, both excellent tissue penetration and rapid blood clearance. Improving the pharmacokinetic characteristics of nanobodies is of great significance to reduce the frequency of drug delivery and drug efficacy. In this review, the biological characteristics of nanobodies were first described, and then the pharmacokinetic characteristics of nanobodies and the methods to further improve the pharmacokinetics were emphatically introduced. On this basis, the research progress of nanobody drugs used for intravenous, subcutaneous, oral and inhalation drug delivery routes was reviewed, the feasibility, safety and therapeutic effect of different drug delivery routes for the treatment of specific diseases were evaluated, and the possible drug delivery routes of nanobodies were also analyzed, so as to provide a reference for the selection of drug delivery routes in the follow-up research and development of nanobody drugs.