Safe, reliable, flexible methods of drug delivery
Protecting macromolecular therapeutics from fast inactivation or degradation within the human body, as well as presenting them to the body in a manner amenable to their interaction and activity (e.g., in case of vaccines, to facilitate specific interactions with immunocompetent cells) is paramount to achieve therapeutic results. In order to achieve these objectives, biomedical scientists have been increasingly relying on the engineering of special delivery vehicles, typically functionalized synthetic polymers, nanoparticles, or liposomes, which are capable of stabilizing and protecting their payload, facilitating their interactions with targeted cells, and, once the mission is accomplished, degrading into benign products. Despite a relatively broad selection of existing carriers, the task of combining multiple biological functionalities and structural characteristics, required for such complex biological undertaking, dictates the need for the development of a new, synthetically versatile and biologically compatible, synthetic platform.
IBBR advances a novel approach to the development of drug delivery carriers utilizing the power of synthetic polyphosphazene chemistry. Polyphosphazenes, a large class of macromolecules based on phosphorus-nitrogen backbone and organic side groups, provide an ideal foundation for the synthesis of biodegradable polymers with a sophisticated set of design parameters. They possess a unique combination of features distinguishing them from other classes of biomedical polymers – high functional density, extraordinary flexibility of the backbone, tunable biodegradation, and unprecedented structural versatility stemming out of their unusual synthetic route. The resulting multifunctionality, ability to spontaneously self-assemble with proteins and biological systems, mimicry of biological materials, and built-in environmental sensitivity provide ample opportunities for the design of smart delivery carriers. Moreover, the synthetic methodologies developed by IBBR scientists allow both the high throughput discovery of new materials and manufacturing friendly processes.
This approach already engendered the development of potent vaccine carriers based on water-soluble ionic polyphosphazenes. They have been proven to display a dramatic immunopotentiating effect in vivo manifested in improved magnitude, quality, onset and duration of immune responses, in addition to the underlying vaccine sparing effect. The lead polyphosphazene adjuvant – poly[di(carboxylatophenoxy)phosphazene], PCPP has been advanced into clinical trials and reported to be safe and immunogenic in humans.
The technology has been further advanced to include important delivery modalities, such as functionalized nanoparticulate assemblies and polyphosphazene microneedles for transdermal delivery of biologics. IBBR is also using its core technology base and scientific expertise to develop new macromolecular systems designed for protein stabilization, evasion of immune system, endosomal escape, and other key features required for the successful delivery of therapeutic agents.