Colloidal gold nanoparticles are targeting probes to improve varlitinib delivery into cancer cells. The nanoconjugates were designed by the bioconjugation of pegylated gold nanoparticles with ...varlitinib via carbodiimide-mediated cross-linking and characterized by infrared and X-ray photoelectron spectroscopy. The drug release response shows an initial delay and a complete drug release after 72 h is detected. In vitro experiments with MIA PaCa-2 cells corroborate that PEGAuNPsVarl conjugates increase the varlitinib toxic effect at very low concentrations (IC50 = 80 nM) if compared with varlitinib alone (IC50 = 259 nM). Our results acknowledge a decrease of drug side effects in normal cells and an enhancement of drug efficacy against to the pancreatic cancer cells reported.
Nanostructure of polysaccharide complexes Coelho, Sílvia; Moreno-Flores, Susana; Toca-Herrera, José L. ...
Journal of colloid and interface science,
11/2011, Letnik:
363, Številka:
2
Journal Article
Recenzirano
Nanoparticles made of gum arabic and chitosan (degree of acetylation 5) at weight ratio of 1 (scale bar=200nm). Display omitted
► Gum arabic–chitosan nanostructures. ► Chitosan degree of acetylation ...(DA) determines the structure of the complexes. ► Gum arabic and chitosan with high charge density (DA 5%) form nanoparticles of 200nm. ► Using chitosan with higher DA (25%), soluble complexes are obtained. ► Soluble complexes are flat when adsorbed on mica surfaces (height⩽10nm).
The interaction of gum arabic (GA) with chitosan (Ch) of different degree of deacetylation was studied by turbidity measurements, dynamic light scattering and atomic force microscopy. The structure of the complexes was found to be directly related to the charge density of chitosan molecules. Gum arabic and chitosan with a degree of deacetylation of 75% form soluble complexes with a loosely globular structure of about 250nm, at weight ratios up to 1.2, if the concentrations are kept low (total biopolymer concentration up to 0.06%). If chitosan has a higher charge density (degree of deacetylation of 93%), colloidal particles are formed, independently of the polymer concentration or ratio. At low concentrations and GA/Ch ratios of 1 or 1.2, the particles have diameters of 200–250nm. The formation of soluble complexes is attributed to a chitosan lower charge density and the presence of non-charged monomers, which prevent the efficient self-assembly of the macromolecules.
Poly(d,l-lactic-
-glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. ...Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms. Thus, new approaches must be envisaged to target GBM tumour cells potentially providing an efficient treatment. Co-delivery of temozolomide (TMZ) and O6-benzylguanine (O6BG), an inhibitor of DNA repair, could provide good therapeutic outcomes. In this work, a fractional factorial design (FFD) was employed to produce an optimal PLGA-based nanoformulation for the co-loading of both molecules, using a reduced number of observations. The developed NPs exhibited optimal physicochemical properties for brain delivery (dimensions below 200 nm and negative zeta potential), high encapsulation efficiencies (EE) for both drugs, and showed a sustained drug release for several days. Therefore, the use of an FFD allowed for the development of a nanoformulation with optimal properties for the co-delivery of TMZ and O6BG to the brain.
Organic–inorganic hybrid nanoparticles are potential effective systems for drug delivery in cancer therapy and diagnosis. Chitosan–gum arabic with entrapped gold nanoparticles were developed as a ...carrier for an anticancer drug bortezomib. The nanosystem was designed to enhance the proteasome inhibitor activity in pancreatic cell lines, S2-013 and hTERT-HPNE. The hydrodynamic diameter of chitosan–gum arabic–gold nanoparticles loaded with bortezomib is around 330 nm. Laser scanning confocal microscopy images show the uptake of the gold nanoparticle/bortezomib encapsulated in chitosan–gum arabic matrix and the fast internalization of these nano combinations into pancreatic cells. Cytotoxic assays assessed that positively charged nanosystems reduce the cell growth and cell proliferation of S2-013s, but the same effect was not observed in cytotoxic response in hTERT-HPNE cells. The outcomes of this study demonstrate the capacity of chitosan–gum arabic nanocarriers to deliver gold nanoparticles/anticancer drug and to increase the permeation and retention effect in S2-013 cells and minimize drug side effects in HPNE cells.
Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, ...plants belonging to
genus and their isolated compounds, such as Parvifloron D, were found to have cytotoxic and antiproliferative activities. However, Parvifloron D is a very low water-soluble compound. Thus, nanotechnology can be a promising delivery system to enhance drug solubility and targeted delivery. The extraction of Parvifloron D from
was optimized through an acetone ultrasound-assisted method and isolated by Flash-Dry Column Chromatography. Then, its antiproliferative effect was selectivity evaluated against different tumor cell lines (IC
of 0.15 ± 0.05 μM, 11.9 ± 0.7 μM, 21.6 ± 0.5, 34.3 ± 4.1 μM, 35.1 ± 2.2 μM and 32.1 ± 4.3 μM for BxPC3, PANC-1, Ins1-E, MCF-7, HaCat and Caco-2, respectively). To obtain an optimized stable Parvifloron D pharmaceutical dosage form, albumin nanoparticles were produced through a desolvation method (yield of encapsulation of 91.2%) and characterized in terms of size (165 nm; PI 0.11), zeta potential (-7.88 mV) and morphology. In conclusion, Parvifloron D can be efficiently obtained from
and it has shown selective cytotoxicity to pancreatic cell lines. Parvifloron D nanoencapsulation can be considered as a possible efficient alternative approach in the treatment of pancreatic cancer.
Gold nanoparticles have become promising vectors for cancer diagnosis and treatment. The present study investigates the effect of bortezomib (BTZ), a proteasome inhibitor, conjugated with pegylated ...gold nanoparticles (PEGAuNPs) in pancreatic and lung cancer cells.
Synthesized gold nanoparticles (PEGAuNPs) were conjugated with bortezomib antitumor drug. We investigated the cytotoxicity induced by BTZ conjugated with functionalized gold nanoparticles in vitro, in the human pancreatic (S2-013) and lung (A549) cancer cell lines.
We found an efficient of conjugation of BTZ with PEGAuNPs. In vitro assays showed that after 72 h' incubation with PEGAuNPs-BTZ cancer cells revealed alterations in morphology; also for S2-013 and A549 cancer cells, the IC50 value of free BTZ is respectively 1.5 and 4.3 times higher than the IC50 value of PEGAuNPs-BTZ. Furthermore, for TERT-HPNE, the IC50 value is around 63 times lower for free BTZ than the conjugated nanovehicle. Cell growth inhibition results showed a remarkable enhancement in the effect of BTZ when conjugated with AuNPs.
Our findings showed that conjugation with PEGAuNPs enhance the BTZ growth-inhibition effect on human cancer cells (S2-013 and A549) and decreases its toxicity against normal cells (TERT-HPNE).
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•Cholesterol and sphingomyelin increase membrane’s complexity, order and rigidity.•Vitamin B12’s affinity for the membrane decreases by increasing its complexity.•The location of ...Vitamin B12 in the membrane enables its binding to the receptor.•Vitamin B12 does not induce changes in the fluidity of the membrane.
Vitamin B12 (VB12) deficiency is one of the most common malnutrition problems worldwide and is related to its poor bioavailability. The lipid composition of cell membranes and molecule-cell membrane lipid interactions are major factors affecting the bioavailability of nutrients. So, the study of these interactions may allow predicting the behavior of VB12 at cellular membranes and the effects on its activity. Thus, lipid vesicles with lipid composition similar to the majority of eukaryotic cell membranes were used as biomembrane models, and their interactions with VB12 molecules were evaluated. For that, different parameters were assessed such as the lipophilicity of VB12, its preferential location in the membrane and its effect on the physical properties of the bilayer. VB12 showed high affinity for the biological membranes, not inducing any biophysical changes in their properties. The interactions of VB12 with the membrane was affected by the complexity of the bilayer, since its increase in order and rigidity hinders the diffusion of molecules. Thus, the low bioavailability of VB12 is not related with its interactions with the biological membranes.
Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were studied as drug delivery vehicles for calcitriol, the active form of vitamin D3. In vitro effects of calcitriol encapsulated in PLGA ...nanoparticles were evaluated with respect to free calcitriol on human pancreatic cell lines, S2-013 and hTERT-HPNE, and the lung cancer cell line A549. Encapsulated calcitriol retained its biological activity, reducing the cell growth. Cytotoxicity assays demonstrated that encapsulation of calcitriol enhanced its inhibitory effect on cell growth at a concentration of 2.4 μM for the S2-013 cells (91%) and for A549 cells (70%) comparared to the free calcitriol results. At this concentration the inhibitory effect on nontumor cells (hTERT-HPNE) decreased to 65%. This study highlights the ability of PLGA nanoparticles to deliver vitamin D3 into cancer cells, with major effects regarding cancer cell cycle arrest and major changes in the cell morphological features.
The aim of this work was to investigate the conformational changes and diffusion of adsorbed proteins (immunoglobulin G (IgG), fibrinogen (Fib) and human serum albumin (HSA)) on hydrophilic quartz ...and hydrophobized quartz (octadecyltrichlorosilane (OTS)) surfaces. Circular dichroism spectroscopy measurements have shown that IgG is the most stable protein after adsorption on hydrophilic quartz, whereas HSA and Fib unfold. The structural changes are dependent on adsorption time, initial protein concentration in bulk, and surface chemistry. The effect of trifluoroethanol (TFE) in recovering the original protein structure after adsorption was analyzed by total internal reflection fluorescence and fluorescence recovery after photobleaching (TIRF-FRAP). TIRF-FRAP experiments revealed a strong dependence of the surface chemistry on protein diffusion coefficients: proteins diffuse 4 times slower on hydrophobic surfaces than on hydrophilic surfaces. The diffusion coefficient of TFE at hydrophobic surfaces is 2 orders magnitude higher than at hydrophilic surfaces. However, protein desorption occurs faster on hydrophilic quartz than on OTS, proving that the strength of protein-surface interaction is weaker at hydrophilic surfaces. This result shows that desorption is determined by surface/protein chemistry and not by mass transfer limitations. FTIR-ATR results demonstrated that TFE interaction with adsorbed proteins is stronger at hydrophilic surfaces than at hydrophobic surfaces.
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