Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma
<b>Background:</b> 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-containin...
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| author | Babita Shashni Hao Thi Tran Long Binh Vong Ren-Jei Chung Yukio Nagasaki |
| author_facet | Babita Shashni Hao Thi Tran Long Binh Vong Ren-Jei Chung Yukio Nagasaki |
| author_sort | Babita Shashni |
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| description | <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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. |
| format | Article |
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| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Pharmaceutics |
| spelling | doaj-art-bf1b9a692908437a918e053b0ba30dc12025-01-24T13:45:43ZengMDPI AGPharmaceutics1999-49232025-01-011715010.3390/pharmaceutics17010050Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung CarcinomaBabita Shashni0Hao Thi Tran1Long Binh Vong2Ren-Jei Chung3Yukio Nagasaki4Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Ibaraki, JapanDepartment of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Ibaraki, JapanSchool of Biomedical Engineering, International University, Ho Chi Minh City 700000, VietnamDepartment of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei 10608, TaiwanDepartment of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Ibaraki, Japan<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/1999-4923/17/1/50oral drug delivery systempolymeric micellessorafenibantioxidant nanocarrierlung cancer |
| spellingShingle | Babita Shashni Hao Thi Tran Long Binh Vong Ren-Jei Chung Yukio Nagasaki Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma Pharmaceutics oral drug delivery system polymeric micelles sorafenib antioxidant nanocarrier lung cancer |
| title | Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma |
| title_full | Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma |
| title_fullStr | Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma |
| title_full_unstemmed | Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma |
| title_short | Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma |
| title_sort | sorafenib loaded silica containing redox nanoparticle decreases tumorigenic potential of lewis lung carcinoma |
| topic | oral drug delivery system polymeric micelles sorafenib antioxidant nanocarrier lung cancer |
| url | https://www.mdpi.com/1999-4923/17/1/50 |
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