Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models

• Published in: International journal of nanomedicine Vol. 11; no. default; pp. 1261 - 1279
• Main Authors: Drewes, Carine C, Fiel, Luana A, Bexiga, Celina G, Asbahr, Ana Carolina C, Uchiyama, Mayara K, Cogliati, Bruno, Araki, Koiti, Guterres, Sílvia S, Pohlmann, Adriana R, Farsky, Sandra P
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2016; Taylor & Francis Ltd; Dove Medical Press
• Subjects: acetyleugenol; Animals; Apoptosis; Apoptosis - drug effects; Aqueous solutions; B16F10 cells; Cancer therapies; Capric/caprylic triglycerides; Caprolactone; Cell Adhesion - drug effects; Cell Movement - drug effects; cell proliferation; Cell Proliferation - drug effects; Cells (Biology); Chemistry; Drug Delivery Systems; Drugs; Flow Cytometry; Health aspects; Humans; Intensive care; lipid-core nanocapsules; Lipids; Lipids - chemistry; Male; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Metastasis; Mice; Mice, Inbred C57BL; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Nanoparticles; Nanotechnology; nanotoxicology; nitric oxide; NMR; Nuclear magnetic resonance; Original Research; Oxidative stress; Particle size; Pharmaceutical sciences; Polyesters - chemistry; SK-Mel-28; Skin cancer; Surface active agents; Toxicity; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; Brazil; United States > US; acetyleugenol; SK-Mel-28; nitric oxide; capric/caprylic triglycerides; cell proliferation; B16F10 cells; mice; nanotoxicology
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S101543

Melanoma is a severe metastatic skin cancer with poor prognosis and no effective treatment. Therefore, novel therapeutic approaches using nanotechnology have been proposed to improve therapeutic effectiveness. Lipid-core nanocapsules (LNCs), prepared with poly(ε-caprolactone), capric/caprylic triglyceride, and sorbitan monostearate and stabilized by polysorbate 80, are efficient as drug delivery systems. Here, we investigated the effects of acetyleugenol-loaded LNC (AcE-LNC) on human SK-Mel-28 melanoma cells and its therapeutic efficacies on melanoma induced by B16F10 in C57B6 mice. LNC and AcE-LNC had z-average diameters and zeta potential close to 210 nm and -10.0 mV, respectively. CytoViva(®) microscopy images showed that LNC and AcE-LNC penetrated into SK-Mel-28 cells, and remained in the cytoplasm. AcE-LNC in vitro treatment (18-90×10(9) particles/mL; 1 hour) induced late apoptosis and necrosis; LNC and AcE-LNC (3-18×10(9) particles/mL; 48 hours) treatments reduced cell proliferation and delayed the cell cycle. Elevated levels of nitric oxide were found in supernatant of LNC and AcE-LNC, which were not dependent on nitric oxide synthase expressions. Daily intraperitoneal or oral treatment (days 3-10 after tumor injection) with LNC or AcE-LNC (1×10(12) particles/day), but not with AcE (50 mg/kg/day, same dose as AcE-LNC), reduced the volume of the tumor; nevertheless, intraperitoneal treatment caused toxicity. Oral LNC treatment was more efficient than AcE-LNC treatment. Moreover, oral treatment with nonencapsulated capric/caprylic triglyceride did not inhibit tumor development, implying that nanocapsule supramolecular structure is important to the therapeutic effects. Together, data herein presented highlight the relevance of the supramolecular structure of LNCs to toxicity on SK-Mel-28 cells and to the therapeutic efficacy on melanoma development in mice, conferring novel therapeutic mechanisms to LNC further than a drug delivery system.