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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