Chitosan-based nano-formulation of berberine isolated from Berberis lycium enhances sustained anticancer effects in MCF-7 cells

Abstract Background Breast cancer remains a major health challenge with limited targeted therapies. Berberine (BBR), an alkaloid from Berberis lycium , has promising pharmacological effects but suffers from poor solubility and bioavailability. This study encapsulates BBR in chitosan nanoparticles to enhance solubility, enable sustained release, and improve its therapeutic efficacy against breast cancer, focusing on its potential mechanism of inducing cell death. Results Berberine (4.2% w/w) was isolated from Berberis lycium from Rajouri, Jammu & Kashmir. The resulting chitosan nanoparticles (BBRC) averaged 114 nm, with a PDI of 0.4, zeta potential of 18.8 mV, 96 ± 3.25% encapsulation efficiency, and 4.8 ± 3.5% loading capacity. MCF-7 breast cancer cell line demonstrated significant sensitivity to BBR (IC₅₀: 8.4 ± 1.4 µg/mL) compared to nano-berberine (IC₅₀: 9.21 ± 2.1 µg/mL) (p < 0.05). In vitro, BBRC showed sustained berberine release over seven days and enhanced effects on MCF-7 cell proliferation, nuclear morphology, cell cycle, and apoptosis compared to free berberine. To the best of our knowledge, this study is among the first to evaluate time-dependent differences between nano- and pure berberine. Docking showed strong binding to MCL-1 (score -7.6 kcal/mol), and ADMET analysis predicted favourable pharmacokinetic and safety profiles for the nano-formulation. Conclusions Chitosan-encapsulated nano-berberine showed enhanced solubility, sustained release, and improved anticancer activity against breast cancer, highlighting its potential as an effective delivery system.