Stefanova Denitsa, Yordanov Yordan, Bogdanova Radostina, Voycheva Christina, Tzankov Borislav, Popova Teodora, Kondeva-Burdina Magdalena, Tzankova Virginia, Toncheva-Moncheva Natalia, Tzankova Diana, Slavkova Marta
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Pharmaceutics. 2025 Mar 4;17(3):331. doi: 10.3390/pharmaceutics17030331.
: Natural substances have been a widely studied source of both pharmaceutical excipients and drugs. Berberine (BRB) is a benzylisoquinoline alkaloid isolated from different plant sources. It possesses various pharmacological properties including antibacterial, antitumor, antidiabetic, neuroprotective, hepatoprotective, anti-inflammatory, antioxidant, etc. However, the limited aqueous solubility hinders its application. Nanosized drug delivery systems are an innovative approach for addressing various challenges regarding drug delivery via different routes of administration. Their utilization could improve the solubility of active constituents. : A melt-emulsification and ultrasonication technique was applied for the preparation of nanostructured lipid carriers (NLCs). They were thoroughly physicochemically characterized by the means of Dynamic Light Scattering, TEM, FTIR, DSC, TGA, and In Vitro release. The In Vitro efficacy and safety were evaluated on cholangiocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, lymphoma, fibroblast, and cardioblast cells, as well as rat liver microsomes by means of cytotoxicity assays and the comet assay. : The obtained nanoparticles had a spherical shape and size around 158.2 ± 1.8 nm with negative zeta potential. They revealed successful drug loading and improved dissolution of berberine in physiological conditions. The In Vitro safety studies showed that loading BRB in NLCs resulted in improved or retained cytotoxicity to tumor cell lines and reduced cytotoxicity to normal cell lines and liver microsomes. The NLC itself increased microsomal malondialdehyde (MDA) and comet formation. : A successful preparation of NLCs with berberine is presented. The nanocarriers show favorable physicochemical and biopharmaceutical properties. The cellular experiments show that the NLC loading of berberine could improve its anticancer efficacy and safety. These findings highlight the potential applicability of berberine in gastrointestinal neoplasms and build the foundation for future practical translation.
天然物质一直是药物辅料和药物的广泛研究来源。小檗碱（BRB）是一种从不同植物来源分离得到的苄基异喹啉生物碱。它具有多种药理特性，包括抗菌、抗肿瘤、抗糖尿病、神经保护、肝脏保护、抗炎、抗氧化等。然而，其有限的水溶性阻碍了它的应用。纳米药物递送系统是一种创新方法，可应对通过不同给药途径进行药物递送的各种挑战。它们的使用可以提高活性成分的溶解度。
采用熔融乳化和超声技术制备纳米结构脂质载体（NLCs）。通过动态光散射、透射电子显微镜、傅里叶变换红外光谱、差示扫描量热法、热重分析法和体外释放对其进行了全面的物理化学表征。通过细胞毒性试验和彗星试验，对胆管癌、结肠腺癌、肝细胞癌、淋巴瘤、成纤维细胞和成心肌细胞以及大鼠肝微粒体进行了体外疗效和安全性评估。
所获得的纳米颗粒呈球形，尺寸约为158.2±1.8nm，zeta电位为负。它们显示出成功的药物负载，并改善了小檗碱在生理条件下的溶解。体外安全性研究表明，将BRB负载到NLCs中可提高或保持对肿瘤细胞系的细胞毒性，并降低对正常细胞系和肝微粒体的细胞毒性。NLC本身增加了微粒体丙二醛（MDA）和彗星形成。
本文成功制备了负载小檗碱的NLCs。纳米载体显示出良好的物理化学和生物药学性质。细胞实验表明，负载小檗碱的NLCs可提高其抗癌疗效和安全性。这些发现突出了小檗碱在胃肠道肿瘤中的潜在适用性，并为未来的实际转化奠定了基础。
