Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

Giardiello, Marco, Liptrott, Neill, McDonald, Tom, Moss, Darren, Siccardi, Marco, Martin, Phil, Smith, Darren, Gurjar, Rohan, Rannard, Steven and Owen, Andrew (2016) Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies. Nature Communications, 7. p. 13184. ISSN 2041-1723

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Abstract

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

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