04:39pm Tuesday 26 September 2017

Sopping Up Proteins With Thermosponges

Boston, MA – 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 protein 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 nanoparticles (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 human growth hormone. 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 therapeutic proteins 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.

This research was supported by the Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C, from the National Heart, Lung, and Blood Institute, National Institutes of Health (CA151884, and NIH R01 grant EB015419-01),  and the David Koch-Prostate Cancer Foundation Award in Nanotherapeutics.

Brigham and Women’s Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham’s medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation’s first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’ Health Studies and the Women’s Health Initiative.  For more information, resources and to follow us on social media, please visit BWH’s online newsroom.

 

 

 

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