小檗碱 (BER) 是从小檗属植物中提取的生物碱，具有广泛的生物活性，包括抗癌。 BER 封装的海藻酸盐 (ALG)/壳聚糖 (CHS) 纳米颗粒 (BER-ALG/CHS-NP) 被开发用于改善乳腺癌的长效治疗。通过缀合反应激活NPs的表面，然后将叶酸（BER-ALG/CHS-NPs-F）接枝到BER-ALG/CHS-NP表面，用于乳腺癌的特异性靶向。 BER-ALG/CHS-NPs-F 通过使用 Expert 设计软件应用 Box-Behnken 设计进行了优化。此外，还对制剂的生物制药性能进行了广泛的体外评估，并测试了细胞活力、细胞摄取和抗氧化活性。在动物身上进行了制剂和游离 BER 的药代动力学比较研究，以评估生物利用度。使用 Malvern Zetasizer 记录的稀释样品的粒径为 240 ± 5.6 nm。 z 电位和预测%包封效率与观察到的 (vs) 分别为 18 mV 和 83.25 ± 2.3% vs 85 ± 3.5%。记录了纳米粒子的高药物释放百分比。使用红外光谱、差示扫描量热法和 X 射线衍射进行的分析研究表明，制剂中各成分的安全组合以及制剂中显示为无定形的药物物理状态。细胞毒性测试表明，与原药相比，该制剂有效降低了受测细胞系的细胞活力和IC50。 BER-ALG/CHS-NPs-F 的细胞摄取比 BER 悬浮液高 5.5 倍。通过 DPPH 测定，BER-ALG/CHS-NPs-F 与 BER-悬浮液的抗氧化能力分别为 62.3 ± 2.5% 和 30 ± 6%，表明叶酸缀合的 NPs 具有良好的自由基清除能力。与 BER 混悬液相比，所开发的制剂的口服生物利用度提高了 4.4 倍。溶血测定表明所开发的制剂对红细胞的破坏<2%。观察到的细胞毒性、细胞摄取、抗氧化活性和吸收改善等实验表征结果表明 BER-ALG/CHS-NPs-F 对乳腺癌的有效性。© 2023 作者。由美国化学会出版。

Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER-ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER-ALG/CHS-NP surface was grafted with folic acid (BER-ALG/CHS-NPs-F) for specific targeting in breast cancer. BER-ALG/CHS-NPs-F was optimized by applying the Box-Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER-ALG/CHS-NPs-F was 5.5-fold higher than that of BER-suspension. The antioxidant capacities of BER-ALG/CHS-NPs-F vs BER-suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER-suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER-ALG/CHS-NPs-F toward breast cancer.© 2023 The Authors. Published by American Chemical Society.