Drug Bioavailability, Stability and Anticancer Effect of Berberine-loaded Magnetic Nanoparticles on MDA-MB-231 Cells in Breast Cancer

Abstract

Introduction: Breast cancer is the most causative factors of death in women. Treatment often consists of surgery, radiation therapy, and chemotherapy, have several side effects. Berberine is an alkaloid naturally-derived from Berberis aristata and a family Berberidaceae exhibits a broad spectrum of pharmacological benefits, including antiviral and anticancer properties etc. The recent development of nanomedicine is an art of delivering drugs to the target-site by improving their safety and efficacy. Among them, Magnetic nanoparticles play a key role to show their targeted drug delivery using a magnetic field. Materials and Methods : In this present study, we fabricated four berberine-loaded magnetic nanoparticles using a modified co-precipitation method with calcination. The resulting BBR/MNPs were characterized using FTIR, XRD, HRSEM, zeta potential, VSM, loading efficiency, stability, and in vitro release studies etc. The most proven MNP formulation type in dissolution was followed by in-vitro anticancer studies on MDA-MB-231 cells. Results and Discussion: XRD, FTIR and TGA results proved that the formed BBR/MNPs were ordered in their structure with iron, silanol groups and berberine moieties. HRSEM reported the average particle size of MNPs 100 to 250 nm after loading with berberine also had a regular spherical shape. The value of the zeta potential was -9 mv and 15 mv at p H 6 for bare MNPs and BBR/MNPs, respectively. Loading efficiency and stability were good at BBR/MCM-41MNP. The saturated magnetization (Ms) value of Fe-MCM-41 MNP (81.76 emu/g) was obtained by VSM analysis. In vitro dissolution studies of four BBR/MNPs were reported at a three different P H 5.5, 6.5, 7.4 including BBR/MCM-41 MNP were 86%, 84% and 82%, respectively. In vitro anticancer studies with BBR/MCM-41-MNP on treated MDA-MB-231breast cancer cells in comparison to standard Doxorubicin. The MTT assay confirmed the cytotoxic effect of BBR/MCM-41-MNP in vitro. The resulting data were statistically analyzed using one-way Anova analysis with n=3 replicates. The IC 50 values (mean standard deviation) of BBR, BBR/MCM-41 MNP and standard doxorubicin were obtained as 16.754± 0.651, 6.750± 0.048, 4.955 ±0.042 µg/ml with significant p<0.0001. Conclusion: The best result was BBR/MCM-41 MNP with an average particle size 50 nm, which showed good drug loading efficiency and size stability above 7 days. Drug release was maximal (86%) at p H 5.5. The MTTassay confirmed that BBR/MCM-41MNP exhibited more cytotoxicity on MDA-MB-231 cells than BBR, MCM-41MNP. The IC 50 of BBR/MCM-41 was close that of standard Doxorubicin. BBR/MCM-41MNP showed optimum drug release with potent anticancer activity along with magnetic targeting.