Nanoparticle-based targeted delivery of therapeutics against arterial media calcification, a major cardiovascular complication in elderly and patients with chronic kidney disease, diabetes and osteoporosis.

Arterial media calcification is a severe cardiovascular complication in elderly and patients with chronic kidney disease (CKD), diabetes and osteoporosis. This disease is a master of camouflage by disguising itself as physiological bone mineralization, which makes it extremely difficult to find efficient and safe therapies against it, i.e. without affecting bone metabolism. The more as CKD and osteoporosis patients already suffer from bone mineralization defects. The candidate's FWO pre-doc project showed for the first time that the ATP analogue ?,?-meATP completely prevented all calcification in vascular smooth muscle cell cultures and efficiently prevented the development of arterial media calcification in rats, however also provoked deleterious effects on bone mineralization. Also other studies performed in the Laboratory of Pathophysiology showed repeatedly that compounds targeting arterial media calcification compromises physiological bone mineralization. Therefore, this FWO Post-doctoral junior project proposal focusses on developing a Poly(lactic-co-glycolic acid) (PGLA) nanoparticle conjugated to anti-elastin antibody drug delivery system to target ?,?-meATP selectively to the blood vessels, bypassing the bone compartment, and increase its bioavailability. PGLA nanoparticles have a high biocompatibility and biodegradability and are FDA approved for human therapy. The nanoparticles will be tested on in vitro and in vivo arterial calcification models.

Keywords:NANOPARTICLES, DIABETES, OSTEOPOROSIS, CHRONIC RENAL FAILURE

Disciplines:Vascular diseases, Molecular physiology, Pathophysiology, Kidney diseases

Project type:Collaboration project