蛋白多肽类药物新型给药系统的研究进展

Research Progress in New Drug Delivery Systems for Proteins and Polypeptides

通过文献检索,对国内外近20年蛋白多肽类药物在纳米粒、脂质体、传递体、微球、水凝胶等新型给药系统的研究按照载体材料、所用技术、性能或给药途径等进行分类介绍,为蛋白多肽类药物新制剂的开发和应用提供参考。结果发现研究较多的蛋白多肽类纳米粒有聚乳酸-羟基乙酸共聚物纳米粒、壳聚糖纳米粒、固体脂质纳米粒和无机纳米粒;脂质体有长循环脂质体、靶向脂质体、长循环靶向脂质体和多囊脂质体;微球有口服微球、注射微球和鼻黏膜给药微球;水凝胶主要为环境敏感型水凝胶,如温度敏感型水凝胶和pH敏感型水凝胶。这些新技术能够在很大程度上提高蛋白多肽类药物的稳定性,延长其体内半衰期,减少给药次数,增加治疗效果,降低药物的毒副作用,实现了该类药物的靶向、缓控释给药。但上述方法也存在一定的局限性,建议进一步加强蛋白多肽类药物的制药新技术、新辅料、新剂型和新给药系统的研究,以便更好的应用于临床。

In order to provide reference for the development and application of new preparations of proteins and polypeptides, the research progress in new drug delivery systems of this kind of drugs was reviewed. Based on document retrieval, references on new drug delivery systems for proteins and polypeptides such as nanoparticles, liposomes, transfersomes, microspheres and hydrogels in recent 20 years were classified and introduced according to carrier materials, technologies, properties or delivery routes. At present, protein and polypeptide nanoparticles which are widely studied include polylactic acid/glycolic acid copolymer(PLGA) nanoparticles, chitosan nanoparticles, solid lipid nanoparticles, and inorganic nanoparticles. Liposomes including long circulating liposomes, targeted liposomes, multivesicular liposomes and flexible nano-liposomes have attracted a lot of attention. For microspheres, injection microspheres, oral microspheres and nasal mucosa microspheres are the focus of research. Hydrogels mainly include environmentally sensitive hydrogels, such as thermosensitive hydrogels and pH-sensitive hydrogels. Besides, transfersomes are also introduced. These new technologies can greatly improve the stability of protein and polypeptide, prolong the half-life in vivo, decrease the times of administration, improve the therapeutic effect, reduce the side effects, and realize targeted, sustained and controlled release delivery of such drugs. However, they all have certain limitations, so the research on new pharmaceutical technologies, new excipients, new dosage forms and new drug delivery systems for proteins and polypeptides should be strengthened, so that more new preparations of this type of drugs can be used in clinical practice.