Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges

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This collaborative project aims to be the first step towards a paradigm change in the use of nanocrystals (NCs), moving from a simple solubility enhancement technique to their application as highly-loaded "Trojan horses" that can cross biological barriers and produce drug accumulation in target tissues or cells. A wide variety of lipid- and polymer-based nanoparticles have been used to target intracellular organelles and specific organs; however, their low drug loading capacity (frequently lower than 10%) pose a significant barrier to further industrial development and translation to bench side products that can actually benefit patients. Therefore, the need for the development of more efficient, highly loaded, targeted nanoparticles is clear. Here, we propose to develop a novel platform, consisting of NCs entirely made of drug, with specifically tailored properties to deliver therapeutic drug concentration to selective tissues. Well-experienced on the use of NCs for enhancing oral, transdermal, and mucosal drug delivery, both in human and veterinary medicine, the applicant's aim is now to develop the next generation of targeted NCs. To this purpose, a major departure on what we know to date about the technology is required. The surface chemistry of the NCs will have to be fundamentally re-thought. Electrostatic and covalent attachment of polymers and specific ligands to the NCs surface will be necessary in order to achieve internalisation by specific cells and permeation across targeted biological barriers. This will increase drug efficacy, selectivity, and contribute to the development of better medicines for patients. Given the multidisciplinary nature of the idea, collaboration with a suitable partner is critical. Prof Marcelo Calderón, a worldwide recognised macromolecular chemist with an extensive track record on functional nanoparticle synthesis, will bring the complementary expertise required to make this project thrive. If successful, this partnership will set the basis of a new, flexible platform with vast therapeutic applications and industrial potential. Our main hypothesis of work relies on the ability of NCs of poorly soluble drugs to remain in the body as undissolved particles for different periods of time. Specifically tailored in terms of size and surface properties, the novel NCs could act as highly loaded nanovectors which can cross biological barriers and produce drug accumulation in target tissues. The general aim of this collaborative project is to develop a new platform based on highly loaded nanoparticles consisting of NCs decorated with ligands enabling active accumulation in target tissues and cells.