Protein nano- or microparticles as artificial inclusion bodies for drug delivery

This research networking center gathers some of the main Spanish research groups in biomedicine, located in more than 100 institutions as universities, hospitals, and technological centers distributed around the country. Bacterial inclusion bodies (IBs) are mechanically stable, insoluble, discrete, and particulate proteinaceous materials produced in recombinant bacteria, with particle sizes ranging from 50 to 1500 nm, and with shapes including cylindrical, amorphous, spherical or ellipsoid. They contain one or few functional protein species (together with other possible components) that can be released intracellularly or extracellularly under physiological conditions, mimicking the functioning of the hormone-releasing human endocrine system. IBs are mechanically stable functional materials that are non-toxic when exposed to cells or to living beings, through oral administration or injection. Because of the combination of mechanical stability and functionality, IBs are then explored as self-immobilized catalysts, showing promises in biotechnological industries and applications. As catalysts, IBs do not pose any regulatory issues and are highly convenient. However, the clinical applicability of IBs is not exempt of drawbacks. They contain irremovable bacterial components at variable composition incompatible with a drug formulation. Moreover, due to the cell factory base, IBs carry on with several homogeneity issues between manufacturing batches. For all these reasons, the provision of alternative structures for delivering proteins of clinical value (hormones, enzymes, etc.) in cells or organs are needed, but the maintenance of the beneficial features of IBs is also desired. In particular, their high penetration to cells, the mechanic stability, and the depot/protein release functions. This new drug-delivery system comprises protein microparticles that mimic the protein release features of IBs (inclusion bodies) and the human hormone secretory system and can be used for the treatment of cancer, and any other pathology requiring intracellular or extracellular protein delivery. These innovative artificial IBs have a slow-release profile of any embedded protein at physiological conditions. The artificial IBs have been prepared in vitro (cell-free engineered) without the presence of bacterial cells, thus in a fully synthetic mode. This protein nano- or microparticles penetrate into cells, thus they can be used as a protein delivery system. The Spanish research center is looking to establish license, research cooperation, or joint venture agreements with industrial partners from the biotech or pharma sector.