Abstract

A series of amphiphilic block and random copolymers based on phenylboronic acid pinacol ester were synthesized via reversible addition–fragmentation chain transfer polymerization. The obtained copolymers can self-assemble in aqueous solution into stable block copolymer nanoparticles and random nanoparticles with sizes of 116.1–158.6 and 126.3–187.0 nm, respectively. All nanoparticles showed hydrogen peroxide (H₂O₂) sensitivity, and the random copolymer nanoparticles presented faster responsiveness to H₂O₂ than did those derived from block copolymers. Berberine (BBR) can be effectively encapsulated into block and random copolymer nanoparticles with loading capacity of 7.6%–9.1% and 7.3%–8.9%, respectively. The BBR release can be controlled in an H₂O₂ medium. For the random copolymer nanoparticles, the release rate of BBR was faster and the cumulative release amounts in response to H₂O₂ were higher over 48 h. The BBR cumulative release amount in the H₂O₂ medium for the block and random copolymer nanoparticles was 62.2%–70.2% and 68.6%–80.4%, respectively. Moreover, good biocompatibility was observed for the BBR-loaded block and random copolymer nanoparticles. BBR and BBR-loaded nanoparticles can improve Glut4 translocation to the cell membrane and promote glucose transport into cells. BBR-loaded nanoparticles can decrease the blood glucose levels in diabetic rats over 15 days. These results imply that the different chain formulation of block and random copolymers affects the H₂O₂ responsiveness and that the two kinds of nanoparticles exhibit potential application as novel vehicles for BBR delivery to regulate blood glucose levels.

摘要

通过可逆加成-断裂链转移聚合合成了一系列基于苯基硼酸频哪醇酯的两亲性嵌段和无规共聚物。所得共聚物可以在水溶液中自组装成稳定的嵌段共聚物纳米颗粒和无规纳米颗粒，尺寸分别为 116.1-158.6 和 126.3-187.0 nm。所有纳米粒子都表现出对过氧化氢 (H ₂ O ₂ ) 的敏感性，无规共聚物纳米粒子对 H ₂ O ₂表现出更快的响应与那些衍生自嵌段共聚物的相比。小檗碱 (BBR) 可以有效地封装成嵌段和无规共聚物纳米粒子，负载能力分别为 7.6%–9.1% 和 7.3%–8.9%。BBR 的释放可以在 H ₂ O ₂介质中控制。对于无规共聚物纳米粒子，BBR 的释放速度更快，并且响应 H ₂ O ₂的累积释放量在48 小时内更高。BBR 在 H ₂ O ₂中的累积释放量嵌段和无规共聚物纳米粒子的介质分别为 62.2%–70.2% 和 68.6%–80.4%。此外，BBR 负载的嵌段和无规共聚物纳米颗粒具有良好的生物相容性。BBR 和 BBR 负载的纳米粒子可以改善 Glut4 向细胞膜的易位并促进葡萄糖转运到细胞中。加载 BBR 的纳米颗粒可以在 15 天内降低糖尿病大鼠的血糖水平。这些结果表明，嵌段共聚物和无规共聚物的不同链配方会影响 H ₂ O ₂响应性，并且这两种纳米颗粒显示出作为 BBR 递送新载体以调节血糖水平的潜在应用。