Zhang Pei, Du Chunyang, Huang Tianhe, Hu Shuai, Bai Yuancheng, Li Cong, Feng Guobing, Gao Yue, Li Zhi, Wang Baoxun, Hirvonen Jouni T, Fan Jin, Santos Hélder A, Liu Dongfei
State Key Laboratory of Natural Medicines, Department of Pharmaceutical Science, China Pharmaceutical University, Nanjing, 210009, China.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, 00014, Finland.
Small. 2022 Apr;18(15):e2200449. doi: 10.1002/smll.202200449. Epub 2022 Mar 1.
A surface adsorption strategy is developed to enable the engineering of microcomposites featured with ultrahigh loading capacity and precise ratiometric control of co-encapsulated peptides. In this strategy, peptide molecules (insulin, exenatide, and bivalirudin) are formulated into nanoparticles and their surface is decorated with carrier polymers. This polymer layer blocks the phase transfer of peptide nanoparticles from oil to water and, consequently, realizes ultrahigh peptide loading degree (up to 78.9%). After surface decoration, all three nanoparticles are expected to exhibit the properties of adsorbed polymer materials, which enables the co-encapsulation of insulin, exenatide, and bivalirudin with a precise ratiometric control. After solidification of this adsorbed polymer layer, the release of peptides is synchronously prolonged. With the help of encapsulation, insulin achieves 8 days of glycemic control in type 1 diabetic rats with one single injection. The co-delivery of insulin and exenatide (1:1) efficiently controls the glycemic level in type 2 diabetic rats for 8 days. Weekly administration of insulin and exenatide co-encapsulated microcomposite effectively reduces the weight gain and glycosylated hemoglobin level in type 2 diabetic rats. The surface adsorption strategy sets a new paradigm to improve the pharmacokinetic and pharmacological performance of peptides, especially for the combination of peptides.
开发了一种表面吸附策略，以实现具有超高负载能力和对共包封肽进行精确比例控制的微复合材料的工程化。在该策略中，将肽分子（胰岛素、艾塞那肽和比伐卢定）制成纳米颗粒，并在其表面用载体聚合物进行修饰。该聚合物层阻止了肽纳米颗粒从油相到水相的相转移，从而实现了超高的肽负载率（高达78.9%）。表面修饰后，所有三种纳米颗粒都有望表现出吸附聚合物材料的特性，这使得能够以精确的比例控制共包封胰岛素、艾塞那肽和比伐卢定。在该吸附聚合物层固化后，肽的释放被同步延长。借助包封，胰岛素单次注射可在1型糖尿病大鼠中实现8天的血糖控制。胰岛素和艾塞那肽（1:1）的共同递送可有效控制2型糖尿病大鼠的血糖水平达8天。每周给予胰岛素和艾塞那肽共包封的微复合材料可有效降低2型糖尿病大鼠的体重增加和糖化血红蛋白水平。表面吸附策略为改善肽的药代动力学和药理性能，特别是肽的组合，树立了新的范例。
