Wu Jun-Zi, Williams Gareth R, Li He-Yu, Wang Dong-Xiu, Li Shu-De, Zhu Li-Min
a College of Chemistry, Chemical Engineering and Biotechnology , Donghua University , Shanghai , P.R. China.
b UCL School of Pharmacy , University College London , London , UK.
Drug Deliv. 2017 Nov;24(1):1513-1525. doi: 10.1080/10717544.2017.1381200.
Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.
制备了多孔聚乳酸 - 乙醇酸共聚物（PLGA）微球，将胰岛素载入其中，然后用聚乙烯醇（PVA）和一种新型含硼酸共聚物[聚（丙烯酰胺苯硼酸 - 共 - N - 乙烯基己内酰胺）；p（AAPBA - 共 - NVCL）]进行包衣。采用层层组装方法在PLGA表面交替沉积PVA和p（AAPBA - 共 - NVCL）涂层来制备多层微球，发现最佳体系是每种涂层各有八层交替。所得材料由具有多孔PLGA核且孔被涂层覆盖的球形颗粒组成。胰岛素能够成功载入颗粒中，载药量和包封率分别达到2.83±0.15和82.6±5.1%，且发现其以无定形形式存在。载胰岛素微球能够根据葡萄糖浓度变化调节药物释放。体外和体内毒理学试验表明它们是安全的且具有高生物相容性。用多层微球治疗糖尿病小鼠时，我们发现它们能在至少18天内有效控制血糖水平，在此期间保持其葡萄糖敏感特性。因此，本研究中开发的新型多层微球作为治疗糖尿病的智能药物递送系统具有巨大潜力。
