Abstract Berberine (BBR) is a naturally occurring plant-derived isoquinoline alkaloid. It has been reported to exhibit multiple pharmacological properties including anticancer activity. However, its low water solubility and bioavailability restrict its clinical use for cancer treatment. Hence, to overcome these limitations and enhance its therapeutic efficacy, in the present study we have encapsulated BBR in Bovine Serum Albumin nanoparticles (BSA NPs) by desolvation method. The average particle size of synthesized nanoparticles were found to be 116 and 166 nm for BSA NPs and BBR-BSA NPs respectively. The FESEM images of nanoparticles implied that prepared nanoparticles are of spherical shape and size was validated. The drug entrapment efficiency of prepared nanoparticles was found to be 85.65 % with a drug loading capacity of 7.78 %. The FTIR spectra, XRD patterns and thermograms of DSC and TGA confirms the synthesis of BBR-BSA NPs and its entrapment in amorphous form. The stability studies of BBR-BSA NPs suggests that nanoparticles were quite stable in aqueous solution of pH 7.4 and degraded under acidic condition (pH 5). The in vitro cytotoxicity assay and Trypan blue assay proved that the prepared BBR-BSA NPs were selectively toxic towards breast cancer cells and kill the cells more efficiently as compared to pure BBR. The cellular uptake studies and AO/EtBr staining suggest that BBR-BSA NPs were therapeutically more effective and improve the anticancer activity of BBR by delivering it to target site, for potential therapeutic use. All the above information collectively suggests that BBR-BSA NPs may emerge as a novel paradigm for treatment of breast cancer.

中文翻译：

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用于有效递送小檗碱的牛血清白蛋白纳米颗粒：制备、表征和体外生物学研究

摘要 小檗碱 (BBR) 是一种天然存在的植物来源的异喹啉生物碱。据报道，它表现出多种药理特性，包括抗癌活性。然而，其低水溶性和生物利用度限制了其在癌症治疗中的临床应用。因此，为了克服这些限制并提高其治疗效果，在本研究中，我们通过去溶剂化方法将 BBR 封装在牛血清白蛋白纳米颗粒 (BSA NPs) 中。BSA NPs 和 BBR-BSA NPs 的合成纳米颗粒的平均粒径分别为 116 和 166 nm。纳米颗粒的 FESEM 图像表明制备的纳米颗粒是球形的，并且尺寸得到验证。发现制备的纳米颗粒的药物包封率为 85.65%，载药量为 7.78%。DSC 和 TGA 的 FTIR 光谱、XRD 图案和热谱图证实了 BBR-BSA NP 的合成及其以无定形形式捕获。BBR-BSA NPs 的稳定性研究表明，纳米颗粒在 pH 7.4 的水溶液中非常稳定，并在酸性条件 (pH 5) 下降解。体外细胞毒性试验和台盼蓝试验证明，与纯 BBR 相比，制备的 BBR-BSA NPs 对乳腺癌细胞具有选择性毒性，并更有效地杀死细胞。细胞摄取研究和 AO/EtBr 染色表明，BBR-BSA NPs 在治疗上更有效，并通过将 BBR 递送到目标部位来提高 BBR 的抗癌活性，用于潜在的治疗用途。所有上述信息共同表明 BBR-BSA NPs 可能成为治疗乳腺癌的新范例。DSC 和 TGA 的 XRD 图案和热谱图证实了 BBR-BSA NP 的合成及其以无定形形式捕获。BBR-BSA NPs 的稳定性研究表明，纳米颗粒在 pH 7.4 的水溶液中非常稳定，并在酸性条件 (pH 5) 下降解。体外细胞毒性试验和台盼蓝试验证明，与纯 BBR 相比，制备的 BBR-BSA NPs 对乳腺癌细胞具有选择性毒性，并更有效地杀死细胞。细胞摄取研究和 AO/EtBr 染色表明，BBR-BSA NPs 在治疗上更有效，并通过将 BBR 递送到目标部位来提高 BBR 的抗癌活性，用于潜在的治疗用途。所有上述信息共同表明 BBR-BSA NPs 可能成为治疗乳腺癌的新范例。DSC 和 TGA 的 XRD 图案和热谱图证实了 BBR-BSA NP 的合成及其以无定形形式捕获。BBR-BSA NPs 的稳定性研究表明，纳米颗粒在 pH 7.4 的水溶液中非常稳定，并在酸性条件 (pH 5) 下降解。体外细胞毒性试验和台盼蓝试验证明，与纯 BBR 相比，制备的 BBR-BSA NPs 对乳腺癌细胞具有选择性毒性，并更有效地杀死细胞。细胞摄取研究和 AO/EtBr 染色表明，BBR-BSA NPs 在治疗上更有效，并通过将 BBR 递送到目标部位来提高 BBR 的抗癌活性，用于潜在的治疗用途。所有上述信息共同表明 BBR-BSA NPs 可能成为治疗乳腺癌的新范例。