journal article·2017-04-05

Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation

Sunandini Chopra, Nicolas Bertrand, Jong-Min Lim, Amy Wang, Omid C. Farokhzad, Rohit Karnik

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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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Advanced Drug Delivery Systems · Nanoparticle-Based Drug Delivery · Drug Solubulity and Delivery Systems

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States

Faculty of Pharmacy, Laval University, CHU de Quebec Research Center, 2705 Laurier Blvd., Quebec City, QC G1V 4G2, Canada

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, United States

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States

Center for Nanomedicine, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, Massachusetts 02115, United States

Department of Chemical Engineering, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do 31538, Korea

Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, United States

King Abdulaziz University, Jeddah, Saudi Arabia

Funding

Canadian Institutes of Health Research · National Institute of Biomedical Imaging and Bioengineering

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