自组装短肽原位凝胶用作蛋白药物载体的初步研究

目的:研究自组装短肽原位凝胶用作蛋白药物载体的可能性。方法:以自组装短肽RAD16-Ⅰ为代表,以溶菌酶为模型蛋白,通过流变学试验表征含蛋白的自组装短肽溶液原位成水凝胶特性,并通过体外试验初步研究蛋白的释放特性。结果:含蛋白的自组装短肽溶液在接触到磷酸盐缓冲溶液后能够迅速形成水凝胶;蛋白容易从中释放并表现出一定的控释作用,8h累积释药量均大于80%,1.5%的RAD16-Ⅰ载蛋白水凝胶24h蛋白累积释药量小于90%;蛋白的结构完整性和活性得到了很好的保持,释放样品中溶菌酶相对活性为98%～115%。结论:自组装短肽具有作为蛋白类药物原位水凝胶载体的潜力。

Study on Self-Assembling Peptide In- Situ Gel as Potential Protein Carrier

OBJECTIVE： To investigate the feasibility of introducing self- assembling peptides as protein drug carrier. METHODS： By using RAD16-Ⅰ as a model of self assembling peptides, lysozyme as the model of protein drug, the property of self-assembling peptide solution containing protein to form hydrogel in- situ were characterized by rheology, and the property of protein release in vitro from self- assembling peptide in- situ hydrogel was studied. RESULTS： The self- as- sembling peptide RAD16-Ⅰ can form hydrogel with certain mechanical intensity rapidly after its solution contained protein being mixed with PBS. Proteins can release easily from RAD16-Ⅰ hydrogel in a sustained- release manner to some extent. About 80% of proteins can be released from the hydrogel within 8 hours and the cumulative protein release from 1.5% hydrogel was less than 90%. The bio- activity of lysozyme released from RAD16- Ⅰ hydrogel was well preserved as 98% to 115%. CONCLUSION： Self-assembling peptide can be employed as potential in- situ hydrogel carrier for protein drugs.