Evaluation of anionic polymer-coated siRNA lipoplexes prepared using a modified ethanol injection method

Area of Science:

• Biotechnology
• Nanomedicine
• Gene Therapy

Background:

• Cationic liposomes are effective carriers for small interfering RNA (siRNA) delivery.
• Previous work developed a modified ethanol injection (MEI) method for preparing cationic siRNA lipoplexes.
• Non-specific interactions of cationic lipoplexes with biological components, like erythrocytes, cause aggregation, hindering intravenous delivery.

Purpose of the Study:

• To evaluate the gene knockdown effect and biodistribution of anionic polymer-coated cationic lipoplexes.
• To investigate the potential of coated lipoplexes for in vivo siRNA delivery.

Main Methods:

• Preparation of cationic lipoplexes using the MEI method.
• Coating cationic lipoplexes with anionic polymers: hyaluronan (HA), chondroitin sulfate (CS), and polyglutamic acid (PGA).
• Evaluation of gene knockdown, cellular association, erythrocyte agglutination, and biodistribution in mice after intravenous injection.

Main Results:

• Anionic polymer coating preserved the gene knockdown effect of cationic lipoplexes.
• Coated lipoplexes showed reduced cellular association compared to uncoated ones.
• Coating with high-molecular-weight HA, CS, and PGA significantly reduced erythrocyte agglutination.
• CS- or PGA-coated lipoplexes exhibited lower pulmonary accumulation and increased hepatic accumulation post-injection.

Conclusions:

• Cationic lipoplexes prepared via MEI can be effectively coated with anionic polymers.
• CS or PGA coating mitigates non-specific interactions with erythrocytes.
• CS- or PGA-coated lipoplexes show promise as vectors for in vivo siRNA delivery to the liver.