重组粒细胞-巨噬细胞集落刺激因子长效、缓释制剂的研究进展

Progress of Long-acting Formulations of Recombinant Granulocyte-Macrophage Colony-stimulating Factor

重组人粒细胞—巨噬细胞集落刺激因子(GM-CSF)临床上有广泛的应用,然而,由于其体内半衰期很短,治疗周期长、不能通过胃肠道屏障进行口服给药,病人必须接受频繁注射。为了减少其注射频率,延长蛋白作用时间,多年来,科学家们对长效GM-CSF的研发进行了多种尝试。这类研究主要集中于三大类:GM-CSF的PEG化、脂质体包封及基于可降解高分子的缓释剂型。然而,这几类方法具有各自优势的同时,也都存在各种不足,如包封率低、对蛋白活性的保护不足、突释问题等。本文将对这三大类针对GM-CSF的长效制剂研究进展的报道,以及各类方法目前存在的主要优缺点进行综述。

Recombinant Granulocyte-Macrophage Colony-stimulating Factor has a wide clinical appfication and has been widely tested as adjuvant in varied kinds of vaccine. However, because of its short plasma half-life and long treatment period, it has to be administrated by frequent injections. Previous attempts to establish satisfactory long-acting and sustained release system loaded with GM-CSF include PEGylation, liposomal carriers, polymer microspheres and matrix etc.. However, there is not yet a product in this category commercially available to date. Although these trials made some improvements in the prolonging of the half-life of bio-macromolecular therapeutic agents in vivo or in the release profile, they all had their own shortages, including the relatively low encapsulation efficiency, the activity loss in formulation steps or the release period, and the burst when they are released from depots. This review will introduce the progress on long-acting formulations for GM-CSF and the advantages and disadvantages of each kind of formulation method.