Purpose: Berberine(BB) is an isoquinoline alkaloid naturally derived from Berberis vulgaris and exerts various pharmacological responses including anticancer activity. Particularly in breast carcinoma, BB has been reported to target multiple pathways ranging from cell cycle arrest to the suppression of angiogenesis to mitochondria-directed apoptosis. However, low bioavailability due to poor solubility limit its clinical application. This obstacle can be surmounted by loading into suitable nanocarrier like liquid crystalline nanoparticles (LCN). Hence, the aim of the present study was to develop and characterize BB-loaded LCN and to evaluate its anticancer activity.
Methods: LCN systems with varied composition of monoolein, poloxamer 407, transcutol® HP (THP) have been prepared by ultrasonication method. The nanoparticles were characterized for size, surface charge, morphology and in vitro drug release followed by cytotoxic assay and cellular uptake.
Results: The mean particle size and polydispersity index was found to be 188.8 ± 0.80 nm and 0.16 ± 0.01. The surface charge of nanoparticle was found to be -9.29 ± 0.68 mV and had demonstrated highest entrapment efficiency (88.14 ± 0.29%), and prolonged release across 24 hours. The nanoparticles were found to be stable maintained during storage at 25°C and 37°C for about 60 days. The IC50 of BB-loaded LCN was about 10-fold lower compared to plain BB, while the IC50 of BB-loaded LCN prepared with THP were about 55-times significantly lower than BB alone. The BB-loaded LCN system demonstrated enhanced in vitro cytotoxicity, enhanced cellular uptake in MCF7 human breast cancer cells as well as in Caco-2 human colonic cell line.
Conclusion: In conclusion, the optimized LCN may be potentially used to enhance oral bioavailability, presenting opportunities as treatment for breast carcinoma.
Yan Shan Loo– School of postgraduate studies, International Medical University, Kuala Lumpur, Kuala Lumpur
Ramkumar Rajendharan– Department of Life Sciences, School of Pharmacy, International Medical Univeristy, Kuala Lumpur, Kuala Lumpur