College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University , Chengdu 610065, China.
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University , Shanghai 200433, China.
ACS Appl Mater Interfaces. 2017 Jul 19;9(28):23428-23440. doi: 10.1021/acsami.7b05740. Epub 2017 Jul 3.
Effective antiosteopenia therapy can be achieved by designing long-term protein/peptide drug delivery systems for bone trabecula restoration. Here we show that a complex of salmon calcitonin and oxidized calcium alginate (sCT-OCA) was prepared and loaded into a thermosensitive copolymer hydrogel for long-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol-gel transition at body temperature. The sustained release of sCT from the in situ gelling system was determined by both the degradation of the hydrogel and the decomposition of the sCT-OCA complex. This system showed sustained effects in reducing serum calcium and bone trabecula reconstruction in the treatment of glucocorticoid-induced osteopenia in rats for approximately 30 days after a single subcutaneous injection, which may shed light on antiosteopenia therapy in the future.
通过设计用于骨小梁修复的长期蛋白质/肽类药物传递系统,可以实现有效的抗骨质疏松症治疗。在这里,我们展示了鲑鱼降钙素和氧化钙藻酸盐(sCT-OCA)的复合物的制备,并将其装载到温敏共聚物水凝胶中用于长期抗骨质疏松症治疗。三嵌段共聚物聚(dl-乳酸-co-乙醇酸)-b-聚(乙二醇)-b-聚(dl-乳酸-co-乙醇酸)(PLGA-PEG-PLGA)在体温下表现出溶胶-凝胶转变。sCT 从原位凝胶系统的释放是由水凝胶的降解和 sCT-OCA 复合物的分解共同决定的。该系统在单次皮下注射后约 30 天内,通过降低血清钙和重建骨小梁,对糖皮质激素诱导的大鼠骨质疏松症具有持续的治疗效果,这可能为未来的抗骨质疏松症治疗提供思路。