Comparison of Bulk and Microfluidics Methods for the Formulation of PLGA Nanoparticles Modified with Cell-penetrating Peptides of Different Architectures


Authors: S. Streck, H. Neumann, H.M. Nielsen, T. Rades, and A. McDowell

Journal: International Journal of Pharmaceutics: X

DOI: 10.1016/j.ijpx.2019.100030

Publication - Abstract

January 31, 2020

Abstract

The efficient and reproducible production of nanoparticles using bulk nanoprecipitation methods is still challenging because of low batch to batch reproducibility. Here, we optimize a bulk nanoprecipitation method using design of experiments and translate to a microfluidic device to formulate surface-modified poly-lactic-co-glycolic (PLGA) nanoparticles. Cell-penetrating peptides (CPPs) with a short, long linear or branched architecture were used for the surface modification of PLGA nanoparticles. The microfluidics method was more time efficient than the bulk nanoprecipitation method and allowed the formulation of uniform PLGA nanoparticles with a size of 150 nm, a polydispersity index below 0.150 and with better reproducibility in comparison to the bulk nanoprecipitation method. After surface modification the size of CPP-tagged PLGA nanoparticles increased to 160–180 nm and the surface charge of the CPP-tagged PLGA nanoparticles varied between −24 mV and +3 mV, depending on the architecture and concentration of the conjugated CPP. Covalent attachment of CPPs to the PLGA polymer was confirmed with FTIR by identifying the formation of an amide bond. The conjugation efficiency of CPPs to the polymeric PLGA nanoparticles was between 32 and 80%. The development and design of reproducible nanoformulations with tuneable surface properties is crucial to understand interactions at the nano-bio interface.

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