Lipid-Polymer Hybrid Chitosan-Stearic Acid Nanoparticles for Efficient Delivery of Berberine to Breast Cancer Cells

Background: Berberine (BBR) is a plant-derived isoquinoline alkaloid extensively studied for its anti-tumor properties. Despite its promising therapeutic potential, the clinical application of BBR has been significantly limited due to challenges such as poor aqueous solubility, suboptimal absorption, and low overall bioavailability. To address these issues, the encapsulation of BBR within nanoparticles (NPs) represents a promising strategy for improving its delivery and efficacy. Methods: In this study, we developed novel lipid-polymer hybrid nanoparticles (LPHNPs) composed of chitosan (CS) and stearic acid (SA), specifically designed for the delivery of BBR to 4T1 breast cancer (BC) cells. The CS-SA NPs were synthesized through an oil-in-water emulsion/ionic gelation technique, optimizing their physicochemical properties for maximum drug encapsulation and release efficiency. Results: The characterization of BBR-loaded CS-SA NPs (CS-SA/BBR NPs) revealed excellent physicochemical attributes, including favorable drug loading capacity and encapsulation efficiency, alongside a controlled release profile of BBR that was markedly slower than that of free BBR. In addition, CS-SA NPs displayed significantly higher in vitro cellular uptake in 4T1 cells. The cytotoxicity evaluation using the MTT assay demonstrated that the blank CS-SA NPs were non-toxic to the 4T1 cell line, indicating their biocompatibility. Additionally, in ovo assessment using the chick chorioallantoic membrane (CAM) assay revealed that CS-SA/BBR NPs significantly inhibited angiogenesis and reduced both the weight and size of tumors compared to treatment with free BBR. Conclusion: Our findings suggest that CS-SA NPs constitute a novel and efficient drug delivery system (DDS) for BBR, enhancing its potential as a therapeutic agent in the management of BC. This encapsulation strategy not only improves the bioavailability of BBR but also minimizes its toxicity, paving the way for further investigations into its clinical application against BC and potentially other malignancies. Future studies should focus on evaluating the long-term efficacy and safety of this nanocarrier system in preclinical models as well as exploring its potential against different types of cancer cells.