A major limitation of protein biologics as drugs is the necessity for frequent parenteral administration. Drug-delivery materials offer a potential solution, but the effectiveness is affected by denaturation caused by protein-material adsorption.
Researchers in the Schneider Lab published in ACS Central Science a new protein delivery platform in which a single subcutaneous administration can be tuned for long-term drug release and there is limited direct contact between globular protein domains and material matrix.
Their strategy utilizes complementary electrostatic interactions made between a suite of designed interaction domains (IDs), installed onto the terminus of a protein of interest, and a negatively charged self-assembled fibrillar hydrogel. These intermolecular interactions can be easily modulated by choice of ID to control material interaction and desorption energies, which allows regulation of protein release kinetics to fit desired release profiles.
In this publication they have shown that this delivery platform can be easily loaded with cargo, is shear-thin syringe implantable, provides improved protein stability, is capable of a diverse range of in vitro release rates, and most importantly, can accomplish long-term control over in vivo protein delivery.
Electrostatically Driven Guanidinium Interaction Domains that Control Hydrogel-Mediated Protein Delivery In Vivo
Stephen E. Miller, Yuji Yamada, Nimit Patel, Ernesto Suárez, Caroline Andrews, Steven Tau, Brian T. Luke, Raul E. Cachau, Joel P. Schneider
ACS Central Science