BackgroundNanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3).ResultsAs a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents.ConclusionsOur results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0241-6) contains supplementary material, which is available to authorized users.
The structural modifications performed and the biological results suggest that the aldehyde and carboxyl groups are relevant to the anti-inflammatory activity in these models.
Background: The biodegradable and biocompatible nature of pectin-based films is of particular interest in wound dressing applications, due to its non-toxicity, pH-sensitivity and gelling activity. An approach to improve the mechanical properties, the release profile of bioactive compounds as well as the performance in wet environments of pectin-based films is mixing with other biopolymers. Objective: To prepare hydrocolloid films based on crosslinked pectin / starch blend loaded with bioactive extracts from leaves of G. tinctoria and U. molinae with controlled release of bioactive compounds and healing property. Method: The hydrocolloid films were characterized by FTIR, SEM, and TGA-FTIR techniques and their tensile properties, water uptake, and polyphenolic release profile in aqueous media were evaluated. The dermal anti inflammatory activity of the hydrocolloid films was assessed by the mouse ear inflammation test. The wound healing property of the loaded hydrocolloid films was explored in a rat model and in a clinical trial (sacrum pressure ulcer). Results: The films showed an adequate water-uptake capacity between 100-160%. The release of active compounds from the hydrocolloid films followed the Korsmeyer-Peppas equation. The mechanical properties of hydrocolloid films were not affected by the plant extracts within the concentration range used. The incorporation of the bioactive extracts in the polysaccharide films inhibited the topical edematous response by about 50%. The topical application of the loaded hydrocolloid film on the pressure ulcer is completely closed after 17 days without showing any adverse reaction. Conclusion: A novel hydrocolloid matrix was produced from crosslinked starch-pectin, which exhibited suitable chemical-physical properties to be used as a carrier of plant extracts with wound healing properties.
Background Gunnera tinctoria has been collected by Mapuche-Pewenche people for food and medicinal purposes. The high polyphenol content of methanolic extract from G. tinctoria leaves with chemical constituents such as ellagic acid and quercetin derivatives suggests its application to prevent endothelial dysfunction and oxidative stress. The aim of this study was to provide evidence of the protective effect of this extract on endothelial function by reducing oxidative stress induced by high d-glucose and H2O2, as well as by stimulating nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs). Results A methanolic extract with a high content of polyphenols (520 ± 30 mg gallic acid equivalents/g dry extract) was obtained from G. tinctoria leaves. Its main constituent was ellagic acid. The results of Ferric reducing antioxidant power and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays of the extract confirmed its antioxidant activity by inhibition pathway of radical species. The incubation of HUVECs with the extract decreased the apoptosis and reactive oxygen species (ROS) synthesis induced by high extracellular concentration of d-glucose or hydrogen peroxide. The extract increased endothelial NO levels and reduced vasoconstriction in human placental vessels. Conclusions This study provides evidence about the antioxidant and endothelial protective properties of methanolic G. tinctoria leaf extract. The extract improves the availability of NO in HUVECs, inhibiting the production of ROS and vasoconstriction.
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