Chitosan Oleate Coated PLGA Nanoparticles as siRNA Drug Delivery System

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• Oligonucleotide therapeutics like miRNAs and siRNAs modulate gene expression but suffer from instability and degradation.
• Viral vectors for gene therapy pose risks including immunogenicity and insertional mutagenesis.
• Non-viral vectors, particularly polymeric nanocarriers, offer a safer alternative for delivering RNA-interfering molecules.

Purpose of the Study:

• To develop and evaluate poly(lactic-co-glycolic acid) (PLGA) core nanoparticles coated with chitosan oleate as carriers for small interfering RNA (siRNA).
• To utilize an siRNA targeting HIV-1 Tat/Rev transcripts as a model for evaluating the nanocarrier system.
• To leverage ionic interactions for efficient siRNA association and protection within the nanocarrier.

Main Methods:

• Fabrication of PLGA core nanoparticles shell-coated with chitosan oleate.
• Association of siRNA targeting HIV-1 Tat/Rev transcripts with the nanoparticles via ionic interactions.
• Evaluation of siRNA protection against nuclease degradation.
• Assessment of cell internalization and cytosolic release of siRNA.

Main Results:

• The PLGA-chitosan oleate nanoparticles successfully encapsulated and protected siRNA from degradation.
• Ionic interactions facilitated efficient siRNA loading onto the positively charged chitosan shell.
• The nanocarrier system demonstrated good cell internalization and effective release of siRNA into the cytoplasm.

Conclusions:

• PLGA-chitosan oleate nanoparticles represent a promising non-viral vector for delivering oligonucleotide therapeutics.
• This system offers enhanced stability, targeted delivery, and efficient intracellular activation of RNA-interfering molecules.
• The developed nanocarrier holds potential for advancing gene modulation therapies, including those against viral infections like HIV-1.