Title : Macrophage-stabilized drug crystals
Abstract:
Poorly soluble drugs with slow rates of clearance are poised to precipitate in the organism following long term oral administration. In this context, my research group has been characterizing the intracellular crystal-like drug inclusions (CLDIs) that are formed by clofazimine, an antimycobacterial drug that is FDA-approved for the treatment of leprosy, and part of the WHO list of essential medications. Using mice as a model organism to study CLDI formation, we have employed X-ray diffraction and other physical methods to elucidate the molecular structure of CLDIs down to the atomic level. In addition, we have biochemically isolated CLDIs from the spleen and livers of drug-treated mice, and have studied the biological effects of CLDIs in relation to soluble clofazimine in vitro and in vivo, demonstrating that CLD is possess potent anti-inflammatory activity. Using synthetic formulations of clofazimine that are designed to resemble CLDIs, we are exploring how biomimetic formulations of macrophage-stabilized drug crystals can be exploited as macrophage targeted, locally active, anti-inflammatory agents. Takeaway Notes • New pharmacokinetic phenomena (insoluble drug complexes). • New tools for studying drug transport from the whole organism down to molecular and atomic level. • New, revolutionary approach to formulation and drug delivery
