糖尿病是一种以高血糖为主要特征的慢性疾病,Ⅰ型或严重的Ⅱ型糖尿病患者往往需要皮下注射胰岛素来维持血糖稳定。由于过量的胰岛素可能导致低血糖,甚至危及生命,因此每日通常需要分2~4次注射,给糖尿病患者的日常生活带来巨大不便。因此,设计具有葡萄糖响应性能的胰岛素递送体系,根据血糖浓度智能地控制胰岛素释放速率,对减少给药次数、方便患者生活具有重要意义。
Figure 1. The designing process of glucose-responsive microneedle patch with enhanced insulin-loading capacity and blood-glucose regulating performance.
Figure 2. (a) Self-assembly of polymers and the INS-loading process. (b) ILCs of the polymers under the feed ratio of 1 g/g. (c) ILCs of PL-NA/FPBA under the feed ratio of 1 g/g. (d) ILCs of PL-NA(20%)/FPBA(38%) under different feed ratios. (e) ILCs (average) of different polymeric carriers in the previous reports. The carriers were labeled according to their main chains, including βCD, Alg, pAsp, HA, CS, Dex, PLGA and αPL. The data of “PL” referred to ILC of PL-NA(20%)/FPBA(38%) under the feed ratio of 2 g/g. The data of (b)-(d) were shown as the means ± SD (n = 3).
Figure 3. The photos and SEM images for (a-d) nNA-MNP and (e-h) NA-MNP. The scale bars were 0.4 mm for (a, e), 0.1 mm for (b, d, f, h) and 1 mm for (c, g).
Figure 4. (a) The reaction between NANP and glucose. (b) The glucose-responsive INS-releasing mechanism of INS/NANP and (c) the corresponding in-vitro cumulative-releasing profiles. (d) The glucose-responsive INS-releasing mechanism of NA-MNP and (e) the corresponding in-vitro cumulative-releasing profiles. The data of (c) and (e) were shown as the means ± SD (n = 3).
Figure 5. (a) The applied MNP on a rat with the skin repairing test (scale bar = 2 mm) and the trypan-blue staining test. (b) The 8-hour BGL-lowering test and (c) the corresponding BGL-lowering speeds (n = 5). (d) The 8-hour curves of plasma INS and (e) the calculation results of AUC (n = 5). (f) The hypoglycemia-avoiding test and (g) the calculation results of AUCHealth control (n = 5). (h) The IPGTT results (n = 5). (i) The curves of plasma INS (n = 5). (j) The BGL-monitoring procedure and (k) the corresponding BGL curves under the “three-meal-per-day” mode (n = 5). The data of (b-i, k) were shown as the means ± SD. The statistical analyses were performed by two-tailed Student’s t-test. The t-test of (h) was applied between “nNA-MNP” and “NA-MNP”. * P < 0.05, ** P < 0.01 and *** P < 0.001.
论文信息:ACS Appl. Mater. Interfaces 2023, 15, 31330-31343
论文链接:https://doi.org/10.1021/acsami.3c06483
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