ABSTRACT
The use of nanoparticles is one of the strategies currently studied to minimize the toxicity and lack of tissue specificity of many cancer drugs used in chemotherapy. In this research the physicochemical and biological behavior of a novel self-assembled nanostructure of the antibiotic Teicoplanin (Teico) was characterized as a nanocarrier system for solubilizing highly hydrophobic drugs like Paclitaxel (Ptx) in aqueous media. The Teico micelles were loaded with Ptx in DMSO or PEG-400. The interaction between the loaded micelles and Albumin human serum albumin (HSA) was then studied by size exclusion chromatography. Transmission electron microscopy, dynamic light scattering and high-resolution liquid chromatography were also used to characterize the physicochemical and structural properties of the micelles to form the Teico/Ptx and Teico/Ptx/HSA micelles. Cellular uptake of Ptx was evaluated by fluorescent microscopy. Thein vitrocytotoxicity of the complexes was studied on Hep-2 tumor cells, by a Crystal Violet assay. Teico cosolvent-free micelles can solubilize up to 20 mg.ml-1of Ptx dissolved in PEG, increasing four times the solubility of Ptx in water compared to Abraxane, and 20 000 times the intrinsic solubility of Ptx in water. In addition, Teico/Ptx micelles binds spontaneously HSA through hydrophobic interaction. Teico and Teico/HSA micelles as a Ptx transporter does not affect its release or biological activity. Therefore, Teico/Ptx or Teico/Ptx/HSA complexes appear as new alternatives for transporting larger amounts of hydrophobic drugs that offer advantages, turning it an interesting option for further study.
Subject(s)
Bridged-Ring Compounds/chemistry , Drug Carriers/chemistry , Glycopeptides/chemistry , Nanoparticles/chemistry , Taxoids/chemistry , Teicoplanin/chemistry , Antineoplastic Agents/chemistry , Cell Line, Tumor , Humans , Micelles , Paclitaxel/chemistry , Particle Size , Polyethylene Glycols/chemistry , SolubilityABSTRACT
Arachis hypogaea L. (Leguminosae) is distributed in tropical and subtropical areas. Peanut has high nutritional and commercial value. Scientific research showed that peanut has biological properties such as anticancer, antioxidant, antiinflammatory. However, it is necessary to know if consumption of peanut, either as food or as a phytopharmaceutical implies a health risk. The aim was to evaluate cytotoxicity and genotoxicity of ethanolic extracts from A. hypogaea. Also, chemical characterization of these extracts was performed. Cytotoxicity was evaluated by MTT and Neutral Red Uptake (NRU) assays on Vero cells. Genotoxicity was studied by Micronuclei and comet assays on Balb/C mice. Qualitative and quantitative chemical analysis of extracts were performed. Results showed that extracts have low cytotoxicity. Tegument ethanolic extract (TEE) and Seed ethanolic extract (SEE) were not genotoxic. The treatments with TEE at 250 mg/kg and SEE at 2000 mg/kg revealed (highest concentrations evaluated) some toxicity on blood marrow cells of mice. Chemical characterization indicated that TEE had 74.33 ± 1.10 mg GAE/g of dried extract and SEE had 15.05 ± 0.06 mg GAE/g of dried extract of total phenolic content. Also, proanthocyanidins (O.D. at 550 nm 1.39 ± 0.15) and caffeic acid (2.46%) were identified in TEE. While, linoleic acid (58.84%) oleic acid (11.31%) and palmitic acid (8.37%) were major compounds of SEE. In conclusion, peanut consumption is safe at concentrations recommended for healthy uses, such as nutrition, and phytomedicine.
