Gelb Madeline B, Maynard Heather D
Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095-1569, USA.
Macromol Mater Eng. 2021 Sep;306(9). doi: 10.1002/mame.202100197. Epub 2021 May 22.
Instability to storage and shipping conditions and injection administration remain major challenges in treating chronic conditions with biopharmaceuticals. Herein, formulations of poly(trehalose methacrylate) (pTrMA) were successfully optimized to stabilize insulin without appreciably increasing viscosity. Polymers were synthesized (2,400 - 29,200 Da), and added to insulin at different concentrations. pTrMA maintained >95% intact insulin against 250 rpm at 37 °C for 3 hours with at least 10 mol. eq. of 5.0 kDa, 7.5 mol. eq. of 9.4 kDa, 5 mol. eq. of 12.8 kDa, 1 mol. eq. of 19.8 kDa, and 0.5 mol. eq. of 29.2 kDa polymers, compared to 13.1% of insulin alone. The lowest pTrMA concentration formulations were more viscous than insulin alone, but the highest viscosity, U-600 with 10 mol. eq. of 5 kDa pTrMA, was only 1.43 cP at 25 °C. This data demonstrates that pTrMA is a promising low viscosity additive to stabilize the diabetes therapeutic insulin.
生物制药在治疗慢性病时，储存、运输条件以及注射给药的稳定性仍是主要挑战。在此，聚甲基丙烯酸海藻糖酯（pTrMA）制剂已成功优化，可在不显著增加粘度的情况下稳定胰岛素。合成了不同分子量（2400 - 29200 Da）的聚合物，并以不同浓度添加到胰岛素中。在37°C、250 rpm条件下，pTrMA在至少10摩尔当量的5.0 kDa、7.5摩尔当量的9.4 kDa、5摩尔当量的12.8 kDa、1摩尔当量的19.8 kDa和0.5摩尔当量的29.2 kDa聚合物存在时，能使>95%的胰岛素保持完整3小时，而单独胰岛素在相同条件下只有13.1%保持完整。最低pTrMA浓度的制剂比单独的胰岛素更粘稠，但粘度最高的含10摩尔当量5 kDa pTrMA的U - 600在25°C时仅为1.43 cP。该数据表明pTrMA是一种有前景的低粘度添加剂，可用于稳定糖尿病治疗药物胰岛素。
