Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery
Yifan Wang,1– 3 Si Chen,1– 3 Xin Yang,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Engineering Research Center of...
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Dove Medical Press
2021-04-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/preparation-optimization-of-bovine-serum-albumin-nanoparticles-and-its-peer-reviewed-article-DDDT |
| _version_ | 1818873677211500544 |
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| author | Wang Y Chen S Yang X Zhang S Cui C |
| author_facet | Wang Y Chen S Yang X Zhang S Cui C |
| author_sort | Wang Y |
| collection | DOAJ |
| description | Yifan Wang,1– 3 Si Chen,1– 3 Xin Yang,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, People’s Republic of China; 3Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, People’s Republic of ChinaCorrespondence: Chunying Cui; Shuang ZhangDepartment of Pharmaceutics, School of Pharmaceutical Science, Capital Medical University, Number 10 Youanmenwai Street, Fengtai, Beijing, 100069, People’s Republic of ChinaTel +86-10-8391-1668; +86-10-8391-1673Fax +86-10-8391-1668; +86-10-8391-1673Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cnBackground: siRNA brings hope for cancer therapy. However, there are many obstacles for application of siRNA in clinical. Because of the excellent biocompatibility, non-toxicity and non-immunogenicity of bovine serum albumin (BSA), BSA-based nanoparticles have been widely designed as a drug carrier system.Methods: The optimal formula for BSA NPs preparation was investigated by central composite design response surface methodology (CCD-RSM), BSA-based survivin-siRNA delivery system (BSA NPs/siRNA) was characterized by dynamic light scattering, atomic force microscope, transmission electron microscope and Bradford method. The in vitro anti-tumor effect and mechanism of BSA NPs were investigated by confocal microscopic imaging, MTT assay, RT-qPCR and ELISA analysis. Moreover, the anti-tumor effect, distribution and biosafety of BSA NPs were studied in vivo.Results: The optimal formula for BSA NPs was settled to be 20 mg/mL for BSA concentration, 9 for pH value, 136% for crosslinking degree and 1.6 mL/min for speed of ethanol addition. BSA NPs/siRNA could remain stable at 4°C for 4 weeks and protect siRNA from degradation by RNase A. Besides, BSA NPs/siRNA could maintain a sustained release of siRNA and promote the uptake of siRNA significantly. The survivin-mRNA level and the survivin-protein level were decreased by 55% ± 1.6% and 54% ± 1.6% separately. The in vivo tumor inhibition results suggested that the tumor inhibition rate of BSA NPs/siRNA-treated group was 54% ± 12% and was similar with that of DOX-treated group (57% ± 9.2%, P > 0.05). The biosafety results confirmed that BSA NPs/siRNA could not induce significant damages to the main organs and blood in vivo.Conclusion: These results demonstrated that CCD-RSM was an effective tool for preparation analysis, and the BSA NPs/siRNA was a promising system for siRNA-based gene therapy.Keywords: bovine serum albumin, BSA, CCD-RSM, survivin-siRNA, nanoparticles, RNAi |
| first_indexed | 2024-12-19T12:58:30Z |
| format | Article |
| id | doaj.art-d31e641ea66d48c489fd7a3e6caee38f |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-19T12:58:30Z |
| publishDate | 2021-04-01 |
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| series | Drug Design, Development and Therapy |
| spelling | doaj.art-d31e641ea66d48c489fd7a3e6caee38f2022-12-21T20:20:20ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-04-01Volume 151531154763908Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA DeliveryWang YChen SYang XZhang SCui CYifan Wang,1– 3 Si Chen,1– 3 Xin Yang,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, People’s Republic of China; 3Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, People’s Republic of ChinaCorrespondence: Chunying Cui; Shuang ZhangDepartment of Pharmaceutics, School of Pharmaceutical Science, Capital Medical University, Number 10 Youanmenwai Street, Fengtai, Beijing, 100069, People’s Republic of ChinaTel +86-10-8391-1668; +86-10-8391-1673Fax +86-10-8391-1668; +86-10-8391-1673Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cnBackground: siRNA brings hope for cancer therapy. However, there are many obstacles for application of siRNA in clinical. Because of the excellent biocompatibility, non-toxicity and non-immunogenicity of bovine serum albumin (BSA), BSA-based nanoparticles have been widely designed as a drug carrier system.Methods: The optimal formula for BSA NPs preparation was investigated by central composite design response surface methodology (CCD-RSM), BSA-based survivin-siRNA delivery system (BSA NPs/siRNA) was characterized by dynamic light scattering, atomic force microscope, transmission electron microscope and Bradford method. The in vitro anti-tumor effect and mechanism of BSA NPs were investigated by confocal microscopic imaging, MTT assay, RT-qPCR and ELISA analysis. Moreover, the anti-tumor effect, distribution and biosafety of BSA NPs were studied in vivo.Results: The optimal formula for BSA NPs was settled to be 20 mg/mL for BSA concentration, 9 for pH value, 136% for crosslinking degree and 1.6 mL/min for speed of ethanol addition. BSA NPs/siRNA could remain stable at 4°C for 4 weeks and protect siRNA from degradation by RNase A. Besides, BSA NPs/siRNA could maintain a sustained release of siRNA and promote the uptake of siRNA significantly. The survivin-mRNA level and the survivin-protein level were decreased by 55% ± 1.6% and 54% ± 1.6% separately. The in vivo tumor inhibition results suggested that the tumor inhibition rate of BSA NPs/siRNA-treated group was 54% ± 12% and was similar with that of DOX-treated group (57% ± 9.2%, P > 0.05). The biosafety results confirmed that BSA NPs/siRNA could not induce significant damages to the main organs and blood in vivo.Conclusion: These results demonstrated that CCD-RSM was an effective tool for preparation analysis, and the BSA NPs/siRNA was a promising system for siRNA-based gene therapy.Keywords: bovine serum albumin, BSA, CCD-RSM, survivin-siRNA, nanoparticles, RNAihttps://www.dovepress.com/preparation-optimization-of-bovine-serum-albumin-nanoparticles-and-its-peer-reviewed-article-DDDTbovine serum albumin (bsa)ccd-rsmsurvivin-sirnananoparticlesrnai |
| spellingShingle | Wang Y Chen S Yang X Zhang S Cui C Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery Drug Design, Development and Therapy bovine serum albumin (bsa) ccd-rsm survivin-sirna nanoparticles rnai |
| title | Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery |
| title_full | Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery |
| title_fullStr | Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery |
| title_full_unstemmed | Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery |
| title_short | Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery |
| title_sort | preparation optimization of bovine serum albumin nanoparticles and its application for sirna delivery |
| topic | bovine serum albumin (bsa) ccd-rsm survivin-sirna nanoparticles rnai |
| url | https://www.dovepress.com/preparation-optimization-of-bovine-serum-albumin-nanoparticles-and-its-peer-reviewed-article-DDDT |
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