Abstract
Nanoparticle (NP) carriers provide new opportunities for controlled delivery of drugs, and have potential to address challenges such as effective oral delivery of insulin. However, due to the difficulty of efficiently loading insulin and other proteins inside polymeric NPs, their use has been mostly restricted to the encapsulation of small molecules. To better understand the processes involved in encapsulation of proteins in NPs, we study how buffer conditions, ionic chelation, and preparation methods influence insulin loading in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) NPs. We report that, although insulin is weakly bound and easily released from the NPs in the presence of buffer ions, insulin loading can be increased by over 10-fold with the use of chelating zinc ions and by the optimization of the pH during nanoprecipitation. We further provide ways of changing synthesis parameters to control NP size while maintaining high insulin loading. These results provide a simple method to enhance insulin loading of PLGA-PEG NPs and provide insights that may extend to other protein drug delivery systems that are subject to limited loading.
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