Desenvolvimento de suspensões de nanocápsulas poliméricas contendo quercetina ou crisina e avaliação biológica em células B16F10 e em modelo de melanoma in vivo

Abstract

Studies have shown that the inflammatory process plays a relevant role in the development of cutaneous melanoma, moment when the immune response is critical, operating to control the development of this pathology and to prevent it from becoming more aggressive. Despite the fact that there is a growing number of studies involving the purinergic system and cancer, there is lack of information about the therapeutic potential of the purinergic system in cutaneous melanoma. Composed by enzymes such as adenosine deaminase (ADA), cell membrane anchored receptors and signaling molecules such as adenosine (ADO), the purinergic system plays a key role in orchestrating events involved in modulating the immune response pattern. Flavonoids, such as chrysin and quercetin, are natural compounds with important anti-inflammatory, antioxidant and anti-tumor properties. In this research, Eudragit® RS100 nanocapsule suspensions containing chrysin or quercetin were developed and showed adequate physicochemical characteristics for colloidal systems such as particle size (582 ± 54 nm; 568 ± 58 nm, respectively), homogeneity of size distribution, total content approximated to the theoretical value, high encapsulation efficiency, and stable up to 14 days of storage. These suspensions were evaluated by in vitro anti-tumor/cytotoxic activity assays and showed decreased viability of B16F10 melanoma cells compared to control at different concentrations of chrysin or quercetin. It was also found that suspensions of nanocapsules, containing or not flavonoids, showed decreased viability of non-tumor cells (murine macrophages; RAW 264.7), however, the nanostructures containing chrysin tended to a cytoprotective effect. After in vitro tests, suspensions were used in an animal model of cutaneous melanoma (C57BL/6 mices) induced through subcutaneous inoculation of B16F10 cell suspension. ADA activity was measured in serum of mices, which developed the tumor and the control animals, after receiving 14-day of oral treatment with the developed nanocapsule suspensions and unencapsulated chrysin and quercetin (7.5 mg/kg). Mices who developed the tumor showed higher ADA activity and suspension of chrysin nanocapsules was able to increase even more ADA activity in an attempt to decrease ADO extracellular levels, since ADO may facilitate tumor development, infiltration and metastasis. Thus, the suspensions developed presented in vitro and in vivo biological activities that corroborate the scientific literature about the potential anti-tumor properties of flavonoids and how these properties can be favored by increasing the bioavailability of these compounds through the incorporation of these substances in nanocarriers.