Sucupira oleoresin-based doxorubicin pH-sensitive nanoemulsions: A potential nanomedicine approach to enhance the safety profile and anticancer activity

Abstract

Plant derivatives-based nanocarriers as a matrix for delivery of chemotherapeutic drugs are capable of enhancing conventional antitumor drugs' cytotoxicity against cancer cells. Bearing in mind that the use of doxorubicin-loaded sucupira oleoresin nanoemulsions can play a significant role in increasing specificity, and efficacy, whilst improvement the chemotherapy safety profile we hypothesize that this nanocarrier may be a powerful alternative strategy for cancer therapy. Thus, the aimed of this research was to prepare and characterize this nanoemulsion, as well as assess the antitumor activity and toxicity in an experimental murine breast cancer model. In the first place, the phytocompounds present in sucupira oleoresin were identified by Liquid chromatography docked Orbitrap-mass spectrometer. Afterward, the doxorubicin-loaded sucupira oleoresin nanoemulsion was prepared using hot homogenization followed by ultrasonic calibration method. Then, nanoemulsions were characterized in terms of mean diameter, polydispersity, zeta potential, entrapment efficiency, and kinetic release. Toxicity and in vivo antitumor activity were also evaluated. The bioactive compounds found in sucupira oleoresin were terpenes, especially sesqui- and vouacapan diterpenes, which have a wide range of biological activities. The sucupira oleoresin nanoemulsions with or without doxorubicin were stable under refrigeration, monodisperse featuring an average size of around 60 nm, and negative zeta potential. High encapsulation doxorubicin content (98 %) was related to the ion-pair formed between doxorubicin and oleic acid. Stability studies in different biological media suggest that the proposed formulation can remain stable after intravenous administration. Meanwhile, the release outcomes indicate a pH-responsive profile. In vivo studies show that nanoemulsions with a combination of doxorubicin and oleoresin exhibit better efficacy and reduced effects on organs of potential toxicity such as the liver, heart, and intestine as well as less body weight loss likened to the free drug. Owing to promising results, we highlight that the doxorubicin-loaded sucupira oleoresin nanoemulsion could supply gain better insights for the combined breast cancer treatment.