An investigation of nano- and micron-sized carriers based on calcium carbonate and polylactic acid for oral administration of siRNA.
Expert Opin Drug Deliv
; 21(8): 1279-1295, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-39141571
ABSTRACT
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 CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution. RESEARCH DESIGN ANDMETHODS:
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 CaCO3 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Particle Size
/
Polyesters
/
Calcium Carbonate
/
Drug Carriers
/
RNA, Small Interfering
/
Nanoparticles
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Expert Opin Drug Deliv
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2024
Document type:
Article
Affiliation country:
Rusia
Country of publication:
Reino Unido