Ternary polymeric nanoparticles for oral siRNA delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Oral delivery of small interfering RNA (siRNA) faces challenges due to poor stability and intestinal absorption.
• Polymeric nanoparticles offer a potential solution for protecting and delivering nucleic acids.

Purpose of the Study:

• To investigate ternary polymeric nanoparticles for enhanced oral siRNA delivery.
• To evaluate the impact of formulation parameters on nanoparticle stability and efficacy.

Main Methods:

• Ternary nanoparticles were formulated using ionic gelation with chitosan derivatives (TMC, TTMC) and anionic components (TPP, HA), encapsulating siRNA.
• Assessed structural stability, siRNA protection, ex vivo intestinal permeability, cellular uptake, gene silencing, and in vivo biodistribution.

Main Results:

• TTMC/siRNA/TPP nanoparticles exhibited excellent structural stability and siRNA protection in simulated intestinal conditions.
• These nanoparticles demonstrated good ex vivo intestinal permeability, superior macrophage uptake, and potent in vitro gene silencing.
• High systemic biodistribution was observed following oral administration of TTMC/siRNA/TPP nanoparticles.

Conclusions:

• TTMC/siRNA/TPP nanoparticles are effective for oral siRNA delivery.
• These nanoparticles show potential as viable vehicles for systemic gene silencing via oral administration.