Biodistribution in vivo

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The CUPIDO final product owns a certain technological complexity because it consists of two parts: the calcium phosphate nanoparticles that act as nano-carrier and the cardiac-specific drug, which needs to be encapsulated inside the nanoparticles. To dissect the biodistribution of each component, in Cupido we decided to first assess the features of each component and later to assess the biodistribution of the full loaded-nanoparticle to ensure that it is the whole product that is able to reach the heart.

Regarding the carrier, the biodistribution of the CaPs nanocarrier has been studied in-vivo up to large animals: in Landrace pigs, three hundred minutes after inhalation of CaP nanoparticles loaded with a marker peptide, a signal was detected in the myocardium, providing evidence for effective delivery of the cargo to the heart (more here).

Z-stack confocal laser scanning microscopy images showing HA peptide in myocardial tissue from pigs treated by CaP-HA inhalation. Immunofluorescence staining for HA (red), LTCC (green), and cell nuclei (DAPI; blue). Scale bar, 20 μm (n = 6).

In the meantime, we have selected the Mimetic Peptide as drug to target the heart due to its ability to improve cardiac contractility in some pathological heart conditions. The therapeutic effect of the peptide was proved by D. Catalucci’s team using a cell-penetrating version of the peptide (R7W-MP). CUPIDO aims to go a step further and test in large animals nanoparticles loaded with the Mimetic Peptide alone, thus without  the cell-internalizing R7W sequence. The efficiency of this drug in rescuing cardiac contractility would then require the CaPs to facilitate its crossing of the pulmonary barrier and subsequent myocardial cell internalization, as already  demonstrated in mice. So far we have collected data on the stability of both the Mimetic Peptideand its cell- penetrating form (R7W-MP) when exposed to plasma from different species,namely mouse, pig and human. These experiments increased our knowledge of the compound for the future in-vivo translation, while ongoing studies are assessing the Mimetic Peptide stability when encapsulated in CaPs.

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