Structurally modified (sm) archeosomes for "stealth" macrophage targeting: first steps towards the efficient design of cardiovascular nanomedicines.

JEREZ HORACIO; BAKAS LAURA; ROMERO EDER

Mar del Plata

Congreso; Reunion Anual de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE)

Developing an anti-atheromatous therapeutic strategy mediated by a nano-drug delivery system capable of recognize and eliminate the foam cells in the atheromatous plaque, constitute a formidable technological challenge. To that aim, a special ?non biological complex drug? (nbcd) has to be designed, capable of circulating for a prolonged time period, minimizing the plasma protein corona -in order to avoid its recognition and elimination by Kupffer cells in the liver-, lacking of any immune reactogenicity, maintaining its colloidal stability during circulation and retaining its active pharmaceutical principle (api) after dilution. Finally, it has to be actively recognised only by its target cells. The importance of this sequence of pre-clinical steps lies in its use as a predictive tool of suitability: failing in accomplishing one single of these requirements means the whole strategy has to be re-designed. In this work, we present for the first time the concept of structural modification of nanovesicles prepared from archaeolipids extracted from the archaea Halorubrum tebenquichense, by inclusion of cholesterol and cholesteryl hemisuccinate in the archaeolipid matrix. The resultant sm-archaeosomes (determined by fluorescence anisotropy of laurdan) were loaded with the bisphosphonate alendronate and tested for their aggregation in blood and plasma of BALB/c mice, retention of alendronate after 1/500 and 1/1000 dilution in blood, and J774A.1/HaCat cells uptake in the absence or presence of blood/plasma. Our results suggest that sm-archaeosomes and conventional archaeosomes or pegylated nanoliposomes, retained drug and colloidal stability in front of a strong dilution, and were actively taken up only by macrophages, the only cell type that received a massive delivery of carried apoptotic drug. Sm-archaeosomes thus, can be presented as the first step towards a macrophage-targeted nano-drug delivery system compatible with industrial scaling up and GMP methods.