State Key Laboratory of Natural Medicines, Department of Pharmaceutical Science, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing, 210009, China.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, 00014, Finland.
Adv Mater. 2023 Jun;35(22):e2211254. doi: 10.1002/adma.202211254. Epub 2023 Apr 7.
Microparticles are successfully engineered through controlled interfacial self-assembly of polymers to harmonize ultrahigh drug loading with zero-order release of protein payloads. To address their poor miscibility with carrier materials, protein molecules are transformed into nanoparticles, whose surfaces are covered with polymer molecules. This polymer layer hinders the transfer of cargo nanoparticles from oil to water, achieving superior encapsulation efficiency (up to 99.9%). To control payload release, the polymer density at the oil-water interface is enhanced, forming a compact shell for microparticles. The resultant microparticles can harvest up to 49.9% mass fraction of proteins with zero-order release kinetics in vivo, enabling an efficient glycemic control in type 1 diabetes. Moreover, the precise control of engineering process offered through continuous flow results in high batch-to-batch reproducibility and, ultimately, excellent scale-up feasibility.
通过控制聚合物的界面自组装，成功地制造出了微粒，使超高药物负载与蛋白质有效载荷的零级释放达到了和谐统一。为了解决它们与载体材料相容性差的问题，将蛋白质分子转化为纳米颗粒，其表面覆盖有聚合物分子。这种聚合物层阻碍了货物纳米颗粒从油相转移到水相，实现了超高的包封效率（高达 99.9%）。为了控制有效载荷的释放，增强了油水界面处的聚合物密度，为微粒形成了一个紧密的外壳。由此产生的微粒在体内能够以零级释放动力学收获高达 49.9%的蛋白质质量分数，实现了 1 型糖尿病的高效血糖控制。此外，通过连续流提供的对工程过程的精确控制实现了高批次间重现性，最终实现了优异的放大可行性。
