Impact of new formulation on mechanical functions of the lungs and their interaction with cells of the immune system after intrapulmonary administration
Olga I. Gusliakova†, Elena N. Atochina-Vasserman‡, Elena Abramova#, Andrew J. Gow#
†Saratov State University, Saratov, Russia.
‡ University of Pennsylvania, Philadelphia, United States of America.
# Rutgers University, Piscataway, New Jersey, United States of America.
Abstract
A study was conducted on the effect of particles and capsules administrated into the lungs on the mechanical properties of the lungs. For this, particles of calcium carbonate (vaterite) coated with polymers (polyargenin / dextran sulfate), the so-called core-shell structures, and capsules consisting of the same polymers were synthesized. These carriers contained in their structure a conjugate of albumin (BSA) and the fluorescent dye Cyanine 7 (Cy7) as a model of a high molecular weight drug. The size of the carriers was 400 ± 60 nm. Two dosages have been tested. FlexiVent equipment was used to determine the mechanical functions of the lungs. 24 hours after intrapulmonary administration of the samples, the following characteristics were determined: maximum inhaled volume (A), elasticity (Cst), area of the P-V loop (hysteresis). The interaction of core-shell structures with alveolar macrophages was also studied. For this, the procedure of bronchoalveolar lavage was carried out 2 and 6 hours after the intrapulmonary administration of coated particles at a dose of 300 * 106 carriers, followed by cell separation by centrifugation. The cells were then stained with antibodies to the following surface proteins: CD11b, F4 / 80, CD11c, CD45, Ly6C. Visualization of the interaction of the core-shell structures containing the BSA + Cy7 fluorescent conjugate was carried out using a laser scanning confocal microscope. The data obtained made it possible to determine the form and dose of drug delivery system, the use of which does not lead to impaired respiratory function. Such carriers turned out to be the core-shell structures at a dose of 30 * 106 carriers. The results of studying the interaction of the administered carriers and alveolar macrophages show that the process of internalization of drug delivery systems into cells began already in the first hours after the intrapulmonary injection.
This work was supported by Scholarship of the President of the Russian Federation.
Speaker
Olga Gusliakova
Saratov State University
Russia
Discussion
Ask question
