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      Is Open Access

      Preparation Optimization of Bovine Serum Albumin Nanoparticles and Its Application for siRNA Delivery

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          Abstract

          Background

          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.

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          Most cited references 49

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          RNA interference is mediated by 21- and 22-nucleotide RNAs.

           S. Elbashir (2001)
          Double-stranded RNA (dsRNA) induces sequence-specific posttranscriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 21- and 22-nt RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3' ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the siRNA-protein complex.
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            Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.

             Felix Kratz (2008)
            Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.
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              Albumin-based nanoparticles as potential controlled release drug delivery systems.

              Albumin, a versatile protein carrier for drug delivery, has been shown to be nontoxic, non-immunogenic, biocompatible and biodegradable. Therefore, it is ideal material to fabricate nanoparticles for drug delivery. Albumin nanoparticles have gained considerable attention owing to their high binding capacity of various drugs and being well tolerated without any serious side-effects. The current review embodies an in-depth discussion of albumin nanoparticles with respect to types, formulation aspects, major outcomes of in vitro and in vivo investigations as well as site-specific drug targeting using various ligands modifying the surface of albumin nanoparticles with special insights to the field of oncology. Specialized nanotechnological techniques like desolvation, emulsification, thermal gelation and recently nano-spray drying, nab-technology and self-assembly that have been investigated for fabrication of albumin nanoparticles, are also discussed. Nanocomplexes of albumin with other components in the area of drug delivery are also included in this review. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                14 April 2021
                2021
                : 15
                : 1531-1547
                Affiliations
                [1 ]Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University , Beijing, People’s Republic of China
                [2 ]Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China , Beijing, People’s Republic of China
                [3 ]Beijing Area Major Laboratory of Peptide and Small Molecular Drugs , Beijing, People’s Republic of China
                Author notes
                Correspondence: Chunying Cui; Shuang Zhang Department 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; +86-10-8391-1673 Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cn
                Article
                299479
                10.2147/DDDT.S299479
                8053787
                © 2021 Wang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 11, Tables: 5, References: 49, Pages: 17
                Funding
                Funded by: National Natural Science Foundation;
                Funded by: Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education;
                Funded by: Capital Medical University, open-funder-registry 10.13039/501100002799;
                Funded by: Beijing Municipal Institutions;
                This work was supported by the National Natural Science Foundation (81502688), Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KM201810025019), and a basic-clinical key research grant (16JL72, 17JL67) from Capital Medical University, the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions (2013–2015).
                Categories
                Original Research

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