Related Experiment Video
Updated: May 30, 2025
Manufacture and Drug Delivery Applications of Silk Nanoparticles
Published on: October 8, 2016
Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma
Babita Shashni1, Hao Thi Tran1, Long Binh Vong2,3
1Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Ibaraki, Japan.
Abstract:
Background: Orally administered sorafenib has shown limited improvement in overall survival for non-small-cell lung cancer patients, likely due to poor pharmacokinetics and adverse effects, including gastrointestinal toxicity. To address these issues, we developed silica-containing antioxidant nanoparticles (siRNP) as a carrier to enhance the therapeutic efficacy of lipophilic sorafenib. Methods: Sorafenib was loaded into siRNP via dialysis (sora@siRNP). The therapeutic efficacy and safety of sora@siRNP (20 and 40 mg-sora/kg) were evaluated in a xenograft mouse model of Lewis lung carcinoma (subcutaneous tumors and experimental metastasis) following oral administration. Results: Crosslinking nanosilica in siRNP improved drug stability, enabling 8.9% sorafenib loading and pH resilience. Oral sora@siRNP exhibited dose-dependent tumor growth suppression by downregulating pMEK, outperforming free sorafenib, which showed inconsistent efficacy likely due to formulation variability. Intestinal damage, a major adverse effect of free sorafenib, was significantly reduced with sora@siRNP, attributed to siRNP's antioxidant property of mitigating oxidative damage. Survival rates in the experimental metastasis model were 66-74% for sorafenib but reached 100% for sora@siRNP, highlighting its superior efficacy and safety. Conclusions: These findings demonstrate that nanosilica-crosslinked antioxidant nanoparticles (siRNP) enhance the stability, delivery efficiency, and safety of lipophilic drugs like sorafenib for oral administration. This platform holds promise for improving therapeutic outcomes in lung cancer while minimizing adverse effects.
Insights
New silica-containing antioxidant nanoparticles (siRNP) significantly improve oral sorafenib delivery for lung cancer, enhancing efficacy and reducing toxicity. This nanoparticle platform offers a promising approach for better cancer treatment outcomes.
Area of Science:
- Nanotechnology
- Materials Science
- Pharmacology
Background:
- Orally administered sorafenib shows limited efficacy in non-small-cell lung cancer due to poor pharmacokinetics and gastrointestinal toxicity.
- Lipophilic drugs like sorafenib require advanced delivery systems to improve therapeutic outcomes.
- Silica-containing antioxidant nanoparticles (siRNP) were developed as a novel carrier for enhanced sorafenib delivery.
Purpose of the Study:
- To develop and evaluate silica-containing antioxidant nanoparticles (siRNP) for oral delivery of sorafenib.
- To assess the therapeutic efficacy and safety of sorafenib-loaded siRNP (sora@siRNP) in a lung cancer mouse model.
- To investigate the potential of siRNP to improve drug stability, reduce toxicity, and enhance survival rates.
Main Methods:
- Sorafenib was loaded into siRNP using a dialysis method, creating sora@siRNP.
- The efficacy and safety of oral sora@siRNP (20 and 40 mg-sora/kg) were tested in a Lewis lung carcinoma xenograft mouse model.
- Tumor growth, metastasis, pMEK expression, intestinal damage, and survival rates were analyzed.
Main Results:
- siRNP demonstrated improved sorafenib stability and pH resilience with 8.9% drug loading.
- Oral sora@siRNP suppressed tumor growth dose-dependently by downregulating pMEK, outperforming free sorafenib.
- sora@siRNP significantly reduced intestinal damage and achieved 100% survival in metastasis models, compared to 66-74% with free sorafenib.
Conclusions:
- Nanosilica-crosslinked antioxidant nanoparticles (siRNP) enhance oral delivery, stability, and safety of lipophilic drugs like sorafenib.
- The siRNP platform shows significant potential for improving lung cancer treatment efficacy while minimizing adverse effects.
- This nanotechnology approach offers a promising strategy for optimizing oral drug delivery in oncology.
