Nanocápsulas caregadas com α, β- amirina: desenvolvimento, caracterização e atividade farmacológica

Abstract

Introduction: It is urgent to elucidate and expand new forms of treatments for diseases such as diabetes, leukemias, prostate cancer, and breast cancer. These are diseases that have a severe impact on the health of men and women around the world. The use of nanotechnology can offer enormous advantages in the effort to develop more effective drugs for these and other diseases. Objectives: This work aimed to evaluate the antileukemic, antitumor, and hypoglycemic activity of polymeric nanocapsules loaded with amyrin. Additionally, the stability in-shelf and the acute oral toxicity of the nanocapsules were evaluated. Methodology: The nanocapsules were synthesized using the polymer deposition method, and then shelf stability was evaluated. The antileukemic effect was evaluated in Jurkat and Molt cells (human acute lymphocytic leukemia), Kasumi-1 (human acute myeloid leukemia), K562 cells (human chronic myeloid leukemia), and C1498 (acute myeloid leukemia). Antitumor activity was evaluated by the MTT method using prostate (PC-3), renal (786-0), hepatic (HepG2), and breast (MCF-7 and MDA-MB-231) cancers. The hypoglycemic effect was evaluated in a streptozotocin-induced diabetes model, using Balb/c mice. Finally, the acute oral toxicity was evaluated by the OECD toxicity class method. Results and discussion: A formulation of spherical nanocapsules with a size of 128.80 nm and a high homogeneity (polydispersion 0.107) was obtained, which maintained its shelf stability for one and a half years. The preparation process had a 65.47% encapsulation efficiency and a load capacity of 2.4 g of amyrin per 100 g of dry nanocapsules. The nanocapsules released 90% of amyrin in 33 minutes, which could improve bioavailability. A strong inhibiting of the growth of PC-3 prostatic tumor cells (GI50 7.00 μg/mL) was observed with a good selectivity index of 3.85. The nanocapsules also showed moderate antiproliferative activity, but with less selectivity, against breast cancer, kidney, and liver cancer cells. The nanocapsules showed good antileukemic activity, with excellent selectivity in the Kasumi-1 cell line (acute myeloid leukemia), inducing cell death through apoptosis, confirmed by caspase cleavages. Neither amyrin nor nanocapsules loaded with amyrins at 10 mg/kg showed hypoglycemic activity. However, at the dose 5 mg/kg, they showed hypoglycemic activity that was not statistically different from the standard drug (acarbose, 100 mg/kg). The nanocapsules, at a dose of 2000 mg/kg in a single dose, showed no signs indicating toxic effects during the 14 days after administration and were classified as "not classified as a toxic substance" according to the OECD 423 criterion. Conclusion: Stable nanocapsules were developed that do not present acute toxicity, and show good antitumor and antileukemic activity, and moderate hypoglycemic activity in rats. Amyrin nanocapsules are a promising product that needs to be further investigated to prove their real utility as antitumor and antileukemic.