An investigation of nano- and micron-sized carriers based on calcium carbonate and polylactic acid for oral administration of siRNA.

Autor: Akhmetova DR; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia.; International Research and Education Centre for Physics of Nanostructures, ITMO University, St. Petersburg, Russia., Rogova A; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia., Tishchenko YA; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia., Mitusova KA; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia., Postovalova AS; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia., Dovbysh OV; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia., Gavrilova NV; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia.; Smorodintsev Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia., Epifanovskaya OS; Laboratory of gene and cell therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia., Pyatiizbyantsev TA; Laboratory of gene and cell therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia., Shakirova AI; Laboratory of gene and cell therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia., Brodskaia AV; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia.; Smorodintsev Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia., Shipilovskikh SA; International Research and Education Centre for Physics of Nanostructures, ITMO University, St. Petersburg, Russia., Timin AS; Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Expert opinion on drug delivery [Expert Opin Drug Deliv] 2024 Aug; Vol. 21 (8), pp. 1279-1295. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1080/17425247.2024.2393244
Abstrakt: Background: Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs' bioavailability. The aim of this work was to investigate the potential of micro- and nano-sized CaCO 3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution.
Research Design and Methods: In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO 3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo .
Results: Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100-250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media.
Conclusion: Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.
Databáze: MEDLINE
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