Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Mater Sci Mater Med. 2012 Apr;23(4):991-8. doi: 10.1007/s10856-012-4568-8. Epub 2012 Feb 25.
The development of peptide drugs and therapeutic proteins is limited by their rapid clearance in liver and other body tissues by proteolytic enzymes, and consequently peptides and proteins are difficult to administer except by injection. There is a growing effort to circumvent these problems by designing strategies to deliver these drugs to specific site of the body. Among them, this peptide carrier presents several advantages for protein therapy including stability in physiological buffer and lack of toxicity. Here, we have been developing a novel bioadhesive polymer matrix that protects entrapped proteins and peptides from degradation by serine protease. Poly(2-lactobionamidoethyl methacrylate-ran-3-acrylamidophenylboronic acid-ran-methoxypolyethylene glycol methacrylate) glycopolymers were synthesized and could self-assemble into the sub-micro particles. The loading capability of insulin, as a drug model, and the insulin release from the particles were assessed. The inhibitory effect of the particles toward trypsin, elastase, and chymotrypsin was evaluated in vitro. Insulin was effectively encapsulated, up to 10%, and could be stained release in vitro. These glycopolymers displayed a strong inhibitory effect toward these exopeptidases. Therefore, novel glycopolymers with excellent inhibitory activity against proteolytic enzymes and reasonable mucoadhesivity might be a useful tool in overcoming the enzymatic barrier to the mucosal delivery (e.g. nasal and buccal) of therapeutic peptides or proteins.
肽类药物和治疗性蛋白质的发展受到其在肝脏和其他身体组织中被蛋白水解酶迅速清除的限制，因此除了注射之外，这些肽类和蛋白质很难被给药。人们越来越努力地通过设计将这些药物递送到身体特定部位的策略来解决这些问题。其中，这种肽载体为蛋白质治疗提供了几个优势，包括在生理缓冲液中的稳定性和缺乏毒性。在这里，我们一直在开发一种新型的生物黏附聚合物基质，以保护包封的蛋白质和肽免受丝氨酸蛋白酶的降解。聚（2-乳酰基乙酰胺基乙基甲基丙烯酸酯-ran-3-丙烯酰胺基苯硼酸-ran-甲氧基聚乙二醇甲基丙烯酸酯）糖聚合物被合成，并可以自组装成亚微颗粒。评估了胰岛素作为药物模型的载药能力和颗粒中胰岛素的释放情况。评估了这些颗粒对胰蛋白酶、弹性蛋白酶和糜蛋白酶的体外抑制作用。胰岛素被有效地包封，高达 10%，并可以在体外染色释放。这些糖聚合物对这些外肽酶表现出很强的抑制作用。因此，具有优异的抑制蛋白酶活性和合理的黏膜黏附性的新型糖聚合物可能是克服治疗性肽或蛋白质经黏膜（例如鼻内和颊部）给药的酶障碍的有用工具。
