In vivo siRNA delivery system for targeting to the liver by poly-l-glutamic acid-coated lipoplex

Results in Pharma Sciences
Yoshiyuki HattoriEtsuo Yonemochi

Abstract

In this study, we developed anionic polymer-coated liposome/siRNA complexes (lipoplexes) with chondroitin sulfate C (CS), poly-l-glutamic acid (PGA) and poly-aspartic acid (PAA) for siRNA delivery by intravenous injection, and evaluated the biodistribution and gene silencing effect in mice. The sizes of CS-, PGA- and PAA-coated lipoplexes were about 200?nm and their ?-potentials were negative. CS-, PGA- and PAA-coated lipoplexes did not induce agglutination after mixing with erythrocytes. In terms of biodistribution, siRNAs after intravenous administration of cationic lipoplexes were largely observed in the lungs, but those of CS-, PGA- and PAA-coated lipoplexes were in both the liver and the kidneys, indicating that siRNA might be partially released from the anionic polymer-coated lipoplexes in the blood circulation and accumulate in the kidney, although the lipoplexes can prevent the agglutination with blood components. To increase the association between siRNA and cationic liposome, we used cholesterol-modified siRNA (siRNA-Chol) for preparation of the lipoplexes. When CS-, PGA- and PAA-coated lipoplexes of siRNA-Chol were injected into mice, siRNA-Chol was mainly observed in the liver, not in the kidneys. In terms of the su...Continue Reading

Citations

Oct 27, 2018·Journal of Cellular Physiology·Khalil HajiasgharzadehBehzad Baradaran
May 29, 2015·The AAPS Journal·Yoon Yeo, Bieong-Kil Kim
Nov 12, 2014·International Journal of Molecular Sciences·Jin SunZongfang Li
Jun 28, 2016·Journal of Liposome Research·Yoshiyuki HattoriHiraku Onishi
Mar 22, 2016·Expert Opinion on Biological Therapy·Ahad MokhtarzadehMohammad Ramezani
Jan 16, 2021·F1000Research·Saffiya HabibMoganavelli Singh
May 12, 2021·Advanced Healthcare Materials·Deidra M WardNicholas A Peppas
Jun 5, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Nidhi RavalRakesh K Tekade

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Methods Mentioned

BETA
dynamic
electrophoresis
transfection
gene knockdown

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