Novel nanoparticle platform proves effective in delivering protein-based drugs

October 22, 2014

( —A research team led by Brigham and Women's Hospital (BWH) has developed and tested a novel nanoparticle platform that efficiently delivers clinically important proteins in vivo in initial proof-of-concept tests. Nanoparticles, which are particles measuring nanometers in size, hold promise for a range of applications, including human therapeutics. The key advantage of the new platform, known as a thermosponge nanoparticle, is that it eliminates the need for harsh solvents, which can damage the very molecules the particles are designed to carry.

The study is published online October 21 in Nano Letters.

"A central challenge in applying nanoparticle technology to therapeutics is preserving proteins' biological activity, which can be inactivated by the organic solvents used in nanoparticle engineering," said Omid Farokhzad, MD, Director of the BWH Laboratory of Nanomedicine and Biomaterials. "Our research demonstrates that the thermosponge platform, which enables the solvent-free loading of proteins, is a promising approach for the delivery of a variety of proteins, including highly labile proteins such as IL-10."

Protein-based therapeutics form an important class of drugs to treat a range of human diseases. However, significant challenges in their development have generally resulted in very slow development paths. To overcome these challenges, Farokhzad and his colleagues sought to create improved nanoparticle methods for delivering protein therapies.

The new thermosponge (TNPs) they developed are composed of biocompatible and biodegradable polymers. These polymers include a central, spherical core, made of the polymer poly(D,L-lactide), and an outer "thermosponge," made of a polaxomer polymer. The core can be either positively or negatively charged, to allow for the delivery of negatively or positively charged proteins, respectively. Importantly, the thermosponge shell can expand or contract as temperatures change, which permits the solvent-free loading of proteins onto the TNP.

The researchers selected a range of different proteins for loading onto the TNPs, including positively-charged interleukin-10 (IL-10) and erythropoietin, and negatively-charged insulin and . The proteins showed similar patterns of sustained release for four days after loading, indicating that the TNPs are able to effectively deliver a variety of proteins.

Further tests showed that the proteins loaded onto the TNPs retained their bioactivity throughout both loading and release from the TNPs.

Importantly, in studies of pre-clinical models, loading of IL-10 or insulin onto the TNPs resulted in dramatic increases in systemic exposure to the proteins, reduced clearance, and increased circulating half-life of the proteins compared to the native protein without TNP.

"The TNPs have been designed and nanoengineered with protein bioactivity in mind, where we optimized a solvent-free nanotechnology that can entrap proteins of various size and charges based on temperature differences into the shell of the nanoparticles. This methodology is amenable for the delivery of a range of and can potentially lead to the facile clinical translation of nanoparticles for biologics delivery," said Won IL Choi, Ph.D., a postdoctoral fellow in the BWH Laboratory of Nanomedicine and Biomaterials.

Explore further: Nanoparticle proteomics: Characterizing protein-nanoparticle interactions in biofluids

Related Stories

Protein glue shows potential for use with biomaterials

August 28, 2014

Researchers at the University of Milan in Italy have shown that a synthetic protein called AGMA1 has the potential to promote the adhesion of brain cells in a laboratory setting. This could prove helpful in improving cell ...

Nanoparticle research and the future of medicine

December 18, 2012

(—A review paper by UCD researchers describing how nanoparticles can gather a cloak of molecules onto themselves in the human body is featured on the front cover of Nature Nanotechnology.

Recommended for you

Nano-decoy lures human influenza A virus to its doom

October 25, 2016

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic ...

New method increases energy density in lithium batteries

October 24, 2016

Yuan Yang, assistant professor of materials science and engineering at Columbia Engineering, has developed a new method to increase the energy density of lithium (Li-ion) batteries. He has built a trilayer structure that ...

Nanofiber coating prevents infections of prosthetic joints

October 24, 2016

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.