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

Abstract

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.

Synthetic scaffolds with full pore interconnectivity for bone regeneration prepared by supercritical foaming using advanced biofunctional plasticizers

“…The characteristic band of aromatic C=C bonds at 1514 cm −1 confirmed the presence of eugenol in the scaffold [41,42]. Eugenol has been reported to act as a solvent of PCL, likely due to electron donor-electron acceptor interactions [43,44]. Nevertheless, the absence of shift of the carbonyl band from PCL (C=O stretching mode, 1700-1750 cm −1 range) with the presence of eugenol in the scaffold formulations indicated that these eugenol-PCL chemical interactions are weak.…”

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

“…These nanocarriers showed efficient brain delivery of drugs as resveratrol [ 37 ] and curcumin [ 38 ] when administered orally and intraperitoneally, as well as the reduction of the side effects of the antipsychotic drug olanzapine [ 39 ]. Furthermore, they demonstrated improved the vitro and in vivo antitumor effectiveness of resveratrol, methotrexate, and acetyleugenol when compared to the free drugs [ 40 , 41 , 42 ].…”

<p>Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature</p>

“… Tumor-bearing BALB/c nude mice after subcutaneous injection of HCC-827 (human lung adenocarcinoma) cells Passive PEGylated lipid based nanosuspention 133 Etoposide i.v. Healthy Kunming mice and tumor-bearing BALB/c mice after subcutaneous injection of A20 (murine lymphoma) cells Passive PCLlipid core nanocarriers 134 Eugenol or acetyl eugenol Orally or i.p. Tumor-bearing C57Bl6 mice after subcutaneous injection of B16F10 (murine melanoma) cells Passive PEGylated lipid squalene nanocarriers 135 Gemcitabine Convection-enhanced delivery (the infusion of therapeutic molecules directly into the brain) Healthy Sprague- Dawley or tumor-bearing Fischer 344 rats after intracranial implantation of RG2 (rat glioma) cells Passive PEGylated PLGA nanoca r riers 136 Glabrescione b i.v.…”