Wednesday, May 24, 2017

Nanoparticles for oral delivery of insulin developed using PolySciTech mPEG-PLGA

Insulin injections are an effective treatment for diabetes, but are painful and difficult to sustain on a constant basis. Insulin cannot, under normal conditions, be ingested for example as a tablet because the protein is very delicate and will be destroyed by stomach enzymes. Loading of proteins into nanoparticles is not a trivial task as many of the solvents used to process nanoparticles would damage proteins causing them to unfold and denature irreversibly. Recently, researchers working jointly at Massachuesettes Institute of Technology (MIT), CHU de Quebec Research Center (Canada), Harvard Medical School, King Abdulaziz University (Saudi Arabia), and Soonchunhyang University (Korea) utilized mPEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AK010) to generate insulin loaded nanoparticles by a zinc precipitation technique. This research holds promise not only to provide for improved insulin therapy with greater patient convenience but also to allow for the loading of other proteins into nanoparticles for therapeutic applications. This work was featured both in a research publication and in a PhD Dissertation. Read more: Chopra, Sunandini, Nicolas Bertrand, Jong-Min Lim, Amy Wang, Omid C. Farokhzad, and Rohit Karnik. "Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation." ACS Applied Materials & Interfaces 9, no. 13 (2017): 11440-11450. http://pubs.acs.org/doi/abs/10.1021/acsami.6b16854, Dissertation: Chopra, Sunandini. "Development of nanoparticles for oral delivery of insulin." PhD diss., Massachusetts Institute of Technology, 2017. https://dspace.mit.edu/bitstream/handle/1721.1/108946/986242657-MIT.pdf?sequence=1


“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. Keywords: biologics; diabetes; insulin; nanomedicine; oral drug delivery; PLGA−PEG nanoparticles; zinc”


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