Nanoparticles based on complex of berberine chloride and polymethacrylic or polyacrylic acid with antioxidant and in vitro antitumor activities

Berberine chloride (Brb) is a natural isoquinoline quaternary alkaloid that displayed a set of beneficial biological properties such as antioxidant, antimicrobial, antitumor, anti-inflammatory, and antiviral. Brb is poorly soluble in water and body fluids and its intestinal absorption is very low, which predetermine its low bioavailability. Polymeric nanoparticles seem to be a good platform to overcome these drawbacks. In this study, for the first time, stable aqueous dispersions of nanoparticles (NPs) based on complexes of Brb and poly(methacrylic acid) (PMA) or poly(acrylic acid) (PAA), were successfully prepared by mixing their dilute aqueous solutions as evidenced by the performed dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. It was found that the mean diameter and zeta potential of NPs depended on the Brb molar fraction. In the case of Brb/PMA and Brb/PAA NPs the encapsulation efficiency was observed to approach a maximum value of 58.9 ± 0.5% and of 78.4 ± 0.9%, respectively, at values of Brb molar fraction at which maximum amount of complexes was obtained. The performed differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses revealed that Brb incorporated in the NPs was in the amorphous state. The Brb release profile was pH-dependent. The Brb-containing NPs displayed good antioxidant capacity close to that of free Brb. In vitro cell viability studies demonstrated that the Brb/PMA (PAA) NPs exerted a higher cytotoxicity against HeLa tumor cell than non-tumor BALB/c 3T3 mouse fibroblast cells. Thus, the obtained NPs are promising candidates in the drug delivery systems in the treatment of cervical tumors.

Keywords: Antioxidant capacity; Antitumor activity; Berberine chloride; Nanoparticles; Poly(acrylic acid); Poly(methacrylic acid).