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Updated: Jun 6, 2025
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery
Thomas Stalder1, Nathan Koenig1, Raphaël Cornu2
1Université de Franche-Comté, CHU Besançon, EFS, INSERM, UMR RIGHT, F-25000 Besançon, France.
Abstract:
Oral administration of siRNA is a challenging strategy for the local treatment of intestinal diseases, including cancer and inflammatory bowel disease. Both nucleic acids and delivery systems, especially lipid nanoparticles (LNPs), are sensitive to the acidic pH of the stomach, bile salts and digestive enzymes. The present work focuses on the design and evaluation of gastroresistant alginate microparticles (MPs) prepared with an original process for oral delivery of siRNA. MPs with a mean diameter of less than 200 µm were obtained without extrusion and emulsification methods. Onpattro® marketed pharmaceutical product and TNF-α siRNA-loaded LNPs were successfully microencapsulated with an efficiency of at least 80 %. Gastroresistance properties and intestinal release were demonstrated in simulated gastric and intestinal fluids. After exposure to simulated gastric fluid, MPs in contact with hepatocyte and LPS-activated monocyte-derived macrophage cell lines reduced the expression of transthyretin and TNF-α, demonstrating the preservation of the siRNA activity.
Insights
Developing gastroresistant alginate microparticles (MPs) enables oral delivery of small interfering RNA (siRNA) for intestinal diseases. These MPs protect sensitive siRNA-loaded lipid nanoparticles (LNPs) from stomach degradation, preserving therapeutic activity.
Area of Science:
- Biotechnology
- Pharmaceutics
- Nanomedicine
Background:
- Oral administration of small interfering RNA (siRNA) for intestinal diseases faces challenges due to degradation in the gastrointestinal tract.
- Lipid nanoparticles (LNPs), common siRNA carriers, are vulnerable to stomach acidity, bile salts, and digestive enzymes.
Purpose of the Study:
- To design and evaluate gastroresistant alginate microparticles (MPs) for the oral delivery of siRNA.
- To encapsulate siRNA-loaded LNPs, including a marketed product (Onpattro®) and TNF-α siRNA, within these MPs.
Main Methods:
- Development of alginate MPs using an original process, achieving a mean diameter under 200 µm without extrusion or emulsification.
- Encapsulation of Onpattro® and TNF-α siRNA-loaded LNPs with high efficiency (≥80%).
- Assessment of gastroresistance and intestinal release in simulated gastric and intestinal fluids.
Main Results:
- Alginate MPs successfully encapsulated siRNA-loaded LNPs with high efficiency.
- MPs demonstrated gastroresistance and controlled release in simulated intestinal conditions.
- Post-gastric exposure, MPs containing siRNA preserved therapeutic activity, reducing target gene expression (transthyretin and TNF-α) in relevant cell lines.
Conclusions:
- Gastroresistant alginate MPs are a viable strategy for oral siRNA delivery to the intestines.
- This formulation protects sensitive siRNA-loaded LNPs from degradation, maintaining their biological activity.
- The developed MPs hold potential for treating intestinal diseases like cancer and inflammatory bowel disease via oral siRNA therapeutics.
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