Preparation, characterization, and evaluation of antitumor effect of Brucea javanica oil cationic nanoemulsions

Abstract

The purpose of this study was to prepare Brucea javanica oil cationic nanoemulsions (BJO-CN) with BJO as drug as well as oil phase and chitosan as cationic inducer, to explore the practical suitability of using cationic nanoemulsions for oral delivery of mixed oil, and to test its bioavailability and antitumor effect. BJO-CN was prepared by chitosan solution stirring method and then characterized physicochemically. The obtained BJO-CN had a spherical morphology with a positive zeta potential of 18.9 mV and an average particle size of 42.36 nm, showing high colloidal stability. The drug loading of BJO-CN was 91.83 mg·mL −1 , determined by high-performance liquid chromatography with precolumn derivatization. Pharmacokinetic studies revealed that, compared with BJO emulsion (BJO-E) (the dosage of BJO-CN and BJO-E was equal to 505 mg·kg −1 , calculated by oleic acid), BJO-CN exhibited a significant increase in the area under the plasma drug concentration–time curve over the period of 24 hours and relative bioavailability was 1.6-fold. Furthermore, the antitumor effect of BJO-CN in the orthotopic mouse model of lung cancer was evaluated by recording the median survival time and the weight of lung tissue with tumor, hematoxylin and eosin staining, and immunohistochemical technique. Results of anticancer experiments illustrated that, even though the administrated dosage in the BJO-CN group was half of that in the BJO-E group, BJO-CN exhibited similar antitumor effect to BJO-E. Moreover, BJO-CN had good synergistic effect in combination therapy with vinorelbine. These results suggested that cationic nanoemulsions are an effective and promising delivery system to enhance the oral bioavailability and anticancer effect of BJO.

The aqueous extract of <em>Brucea javanica</em> suppresses cell growth and alleviates tumorigenesis of human lung cancer cells by targeting mutated epidermal growth factor receptor

“…One of the major components in the aqueous BJ extract, brusatol, is capable of overcoming drug resistance by decreasing nuclear factor erythroid 2 p45-related factor 2, thereby enhancing the cytotoxic effect of numerous chemotherapeutic agents 23. A report showed that cationic nanoemulsions of BJ oil mixture can be an effective delivery system that enhances the oral bioavailability with promising anticancer prospect 24. A recent study has proven that aqueous extract of the BJ plant suppressed the growth of liver cancer by reducing cell proliferation and activating apoptosis 14.…”

<p>Pharmacokinetic studies of nanoparticles as a delivery system for conventional drugs and herb-derived compounds for cancer therapy: a systematic review</p>

“…The AUC of BJO-CN was increased by 1.6-fold, and the t 1/2 was prolonged by 1.3-fold compared with BJO emulsion. CN has been demonstrated as a promising drug delivery system and has the potential to reduce the required frequency of BJO dosing 48. Genistein (Gen), an active compound found in soybeans, exerted its anticancer activity by inducing apoptosis through inhibiting tyrosine kinases and NF-κB.…”

Improved delivery of natural alkaloids into lung cancer through woody oil-based emulsive nanosystems

“…In addition, EFEN had a lower negative zeta potential (∼−1 mV), which caused it to experience less repulsion force from the negatively charged cell membrane. It has been reported that nanosystems are sometimes designed as cationic formulations in order to decrease repulsion (Liu et al., 2016 ). EFEN enhanced the mobility through cellular membranes by using liquid emulsion nanosystems that contained liquid components such as oil and surfactants (Ganta et al., 2014 ).…”