Design, formulation, biopharmaceutical evaluation and in-vitro screening of boldine phytosomes for breast cancer therapy

Abstract

Boldine ((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine) is an aporphine alkaloid identified in high concentrations in the bark and leaves of the boldo (Peumus boldus Mol.), tree in Chile. Until recently, anticancer drugs were mostly derived from plants. This research set out to develop and optimize Boldine Phytosomes formulation by conducting 17 runs of a three-factor, three-level box-Behnken design (Boldine-PHY). Compared to naturally occurring chemicals, phytosomes are more easily accessible due to their enhanced capacity to permeate through bio membranes and reach systemic circulation. The formulations effectiveness was evaluated using various parameters including vesicular size, entrapment efficiency, PDI, zeta potential, and in-vitro release. The entrapment effectiveness of the optimized formulation was 89.34 ± 2.05%, the PDI was 0.114 ± 0.15, and the size of the vesicles was 123.7 ± 3.06 nm (F8), zeta potential of 33.493.49 mV and a drug release of 63.58 ± 4.1% obtained in 24 h. The pH, viscosity, homogeneity, and drug concentration of an optimized Phytosomal formulation (F8) gels made with 1% Carbopol 934 were evaluated. In addition, studies on Phytosomal gel and formulation indicated three months of shelf life. Boldine phytosomes showed a modest cytotoxicity impact of 78.36 ± 2.58 µg/mL in in vitro experiments, whereas doxorubicin was at 58.35 ± 3.5 µg/mL and Phytosomal gel was at 203.57 ± 1.3 µg/mL. At an inhibitory concentration of 8.62 ± 3.04 µg/mL and a selectivity index greater than 3, Phytosomal gel showed the greatest anti-proliferative action on 4 T1 cancer cells. The results showed that phytosomes are much better than Phytosomal gel and doxorubicin. The in vivo investigation showed the safety of phytosomal gel at a dose below 2000 mg/kg. Phytosomal gel seems to have considerable potential as a drug delivery and treatment formulation for breast cancer.