Desenvolvimento, caracterização e avaliação antitumoral de nanoemulsões o/a contendo óleo de andiroba e doxorrubicina.

Abstract

Cancer is a globally impactful disease, characterized by high incidence and mortality rates. Among the various types, breast cancer stands out for its significant heterogeneity, with particular emphasis on triple-negative breast cancer (TNBC), which presents the worst prognosis due to its aggressive nature. Breast cancer treatment is highly individualized and, in most cases, includes systemic therapies such as chemotherapy. Doxorubicin is one of the main drugs used in the treatment of TNBC, known for its effectiveness, although its use is limited by adverse effects, especially cardiotoxicity. In this context, nanotechnology emerges as a promising strategy to mitigate these side effects. Nanoemulsions stand out as drug delivery systems capable of promoting controlled drug release, thereby enhancing therapeutic efficacy and reducing toxicity. Additionally, these systems allow the incorporation of vegetable oils, which may enhance therapeutic effects through anti-inflammatory or pro-inflammatory actions. An example is andiroba oil, widely recognized for its anti-inflammatory and cytotoxic properties, and of great relevance within the national context. Therefore, this study evaluated the encapsulation of doxorubicin in nanoemulsions containing andiroba oil in order to assess the influence of this nanosystem on antitumor activity in an experimental model of murine triple-negative breast cancer (4T1). The nanosystems were developed using an ion-pairing strategy with doxorubicin, employing two ionic pairs (α-tocopherol succinate and oleic acid), which contributed to prolonged drug release in acidic environments. Physicochemical characterization revealed an appropriate particle size (around 100 nm for both nanoemulsions), along with good stability, low particle aggregation, and proper dispersion (PDI around 0.2), and maintenance of encapsulation efficiency at approximately 95% after 90 days of analysis, factors that support prolonged therapeutic effects. Moreover, preliminary safety studies showed that the nanoemulsions caused less cardiotoxicity compared to free doxorubicin. Finally, in vivo tests indicated a significant reduction in tumor volume and metastases, as well as evident cardiac protection. These findings reinforce the potential of andiroba oil-based nanoemulsions as an effective and safe therapeutic alternative to optimize the use of doxorubicin in the treatment of triple-negative breast cancer.