蛋白多肽类药物的高分子载体材料研究进展

Research Progress of Polymer Material Carrier for Protein and Peptide Drugs

蛋白多肽类药物是指能影响和调节机体生理、生化和病理过程,用以诊断、预防和治疗的内源性生物大分子。具有原料简单易得、特异性强、使用剂量少、毒性低、治疗效果显著等优点。但是此类药物的稳定性差,生物半衰期较短,为维持疗效,将此类药物制成缓释药物传递系统,来保护其结构稳定,提高给药效率,并实现靶向给药,选取优良的载体是十分重要的。文章就蛋白质多肽类药物缓释传递系统的载体材料进行了概述,表明合成高分子材料比天然来源聚合物和无机物更具有优势,同时对比了几种常用的合成高分子材料如聚乳酸,聚乳酸-羟基乙酸共聚物,聚己内酯等用于载蛋白多肽类药物的优缺点,以期为后续研究提供参考。

In recent years,protein therapeutics are increasingly used for treatment of many diseases.This trend lights on the significant role of protein and peptides drugs in the development of drugs.Currently FDA has approved over 30 different recombinant DNAderived proteins,e.g.erythropoietin,interferon alpha-2a / b,somatropin and follitropin beta and many more are in a far stage of development.Protein and peptide drugs have high specificity and activity at relatively low concentrations,and have low toxicity,in comparison with small chemical drugs.These features have made protein and peptide drugs indispensable in combating human diseases.However,many protein and peptide drugs are degraded by proteolytic enzymes,and can be rapidly cleared by kidneys,generate neutralizing antibodies and have a short circulating half-life and low solubility.To overcome these drawbacks,development of suitable drug delivery systems is a major issue.The development of delivery systems and their evaluation for therapeutic proteins depend on biophysical,biochemical and physiological characteristics of protein and peptides molecules,including their molecular size and biological half life.With the advent of microspheres,microcapsules,liposomes,hydrogels and other technology,the problem of protein and peptide drugs can be effectively solved,including inactivation in the gastrointestinal tract and poor bioavailability of the drug.Some biodegradable polymers such as polyesters have already been employed as excipients in pharmacology.Selecting the appropriate carrier material is very important,which can effectively improve the efficiency of administration of these drugs,protect its structural stability,and achieve targeted drug delivery.The carrier material of peptides and protein drugs have been summarized,indicating that synthetic polymer material has more advantages than natural polymers and inorganic sources.Then several common used synthetic polymer materials（such as PLA,PLGA,PCL,and so on） are compared so as to provide a reference for future study.