A group of researchers at Harvard Medical School has developed a strongly cationic nanoparticle that physically absorbs proteins to form a new type of drug-carrier complex in aqueous solution.
The scientists say the new platform carries a hefty number of proteins per particle, over 20% by weight, which boosts the therapeutic dose. And little or no organic solvents are used, which prevents protein denaturation.
The researchers described in the journal Angewandte Chemie how the proteins attach to the PLGA-polycation nanoparticle in solution through electrostatic interactions by mixing and forming nanosphere complexes.
“Its just like the way fluff attaches to clothes or gloves in winter. So this is about using nanoparticles to absorb large amounts of proteins via charge interactions, in aqueous solutions without organic solvents, and it happens in seconds,” said Jun Wu of Brigham and Women’s Hospital, Harvard Medical School.
“The nanoparticles themselves are made of some amino acids and FDA-approved polymers, so they are totally biocompatible and are safe in the human body.”
PLGA-based nanoparticles have been widely used due to their biocompatibility, biodegradability, small particle size and high drug-loading capacity. Most nanoplatforms are able to have some proteins absorbed or embedded in the nanoparticle, but this approach is superior, said Wu, who describes it more like peanuts smothered in chocolate, the latter being the proteins.
“We can load a large amount of proteins onto a single nanoparticle, which means that the anti-cancer efficacy or therapeutic efficacy could be high for each nanoparticle, so we call it a protein bomb,” said Wu.
“[They] have begun to address a critical topic in the 'drug' delivery field, which is how to best deliver some of the most evolved molecules known, namely proteins. A very large and growing fraction of pharma today is focused on proteins and peptides, but these large molecules have issues of stability as well as delivery to the right place in the body,” added nanobiopolymer expert Dennis E. Discher at the University of Pennsylvania.
“Farokhzad and coworkers describe a fascinating polymer assembly approach to the problem and include initial studies with cells in culture. I look forward to seeing the next exciting phase of this work in vivo.”
The group has been working on new generations of the protein nanocarriers and has looked at including insulin for cardiovascular diseases and other proteins for immunotherapy. The aim is also to make reformulations of the drug-nanoparticle complex as straightforward as possible, so that someone without scientific training could follow a simple recipe.
The scientists mixed poly(lactide-co-glycolic acid), or PGLA, and L-arginine-based polycations (PC) to generate a block co-polymer, which combined to produce the nanoparticle bomb.