Polysaccharide nanoparticles were studied as drug delivery vehicles for chemopreventive agents.
Green tea polyphenol epigallocatechin-3-gallate (EGCG) was incorporated into a carbohydrate matrix of ...gum arabic and maltodextrin with an encapsulation efficiency of approximately 85%.
Encapsulated EGCG retained its biological activity, reducing the cell viability and inducing apoptosis of Du145 prostate cancer cells. Clonogenic assay demonstrated that encapsulation of EGCG enhanced its inhibitory effect on cell proliferation (10-20%) at lower concentrations (1-2 µM), compared with free EGCG.
This study highlights the use of polysaccharide nanoparticles in chemoprevention as they can be used to deliver natural antioxidants capable of inhibiting steps of the tumorigenesis process.
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•Immuno nanoparticles enhance the BBB permeability for encapsulated peptides.•The cellular uptake of PLGA immuno nanoparticles corroborates a saturation mechanism.•PLGA nanoparticles ...show a high efficiency to entrap the peptide iAβ5.•In vitro assays show an enhanced concentration of targeted carriers into the cells.
During the last few decades, relevant efforts have been reported to design nanocarriers for drug transport through the blood brain barrier (BBB). New drugs, such as peptide iAβ5, capable to inhibit the aggregates associated with Alzheimeŕs disease (AD) are being tested but the most frequent drawback is to reach the brain in the desired concentrations due to the low BBB permeability-surface area. Our approach, as a proof of concept to improve drug transport through the BBB, is based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles with surface functionalized with anti-transferrin receptor monoclonal antibody (OX26) and anti-Aβ (DE2B4) to deliver encapsulated iAβ5 into the brain. Porcine brain capillary endothelial cells (PBCECs) were used as a BBB model to evaluate the system efficacy and toxicity. The uptake of immune nanoparticles with a controlled delivery of the peptide iAβ5 was substantially increased compared to the nanoparticles (NPs) without monoclonal antibody functionalization.
In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of ...the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (
T
1
). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer.
Structure of Bortezomib loaded, surface functionalized Au nanoparticles.
Liposomes modified with anti-amyloid (19B8) and anti-transferrin receptor (OX26) monoclonal antibodies through the coupling reagents maleimide and biotin-streptavidin system.
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...•Immunoliposomes for peptide delivery to brain areas affected by amyloid are proposed.•The cellular uptake depends on the cross linker used for liposome surface decoration.•Bulky ligands between the liposome surface and antibody are more efficient.•In vivo assays show an enhanced concentration of the targeted carriers in rat brains.
Drug delivery systems that can reach brain areas affected by amyloid deposits are still underdeveloped. We propose pegylated liposomes functionalized with two antibodies, the anti-transferrin receptor monoclonal antibody (OX26MAb) and the anti-amyloid beta peptide antibody (19B8MAb), as nanocarriers of drugs for Alzheimer’s disease therapy. Two distinct conjugation methods are investigated. In one formulation, the OX26MAb is conjugated to the tip of polyethylene glycol molecules through the maleimide group and the 19B8MAb is bound through the streptavidin–biotin complex. In the second system the conjugation reagents are swapped between the antibodies. Fluorescence spectroscopy experiments on porcine brain capillary endothelial cells show that the cellular uptake of the immunoliposomes is substantially more efficient if OX26MAb antibody is conjugated through the streptavidin–biotin complex instead of the maleimide group. The ability of the immunoliposomes to cross the blood brain barrier was established by in vivo studies in wild type rats. Our results demonstrate the importance of the conjugation method used to bind the antibody that targets the blood brain barrier to immunoliposomes for efficient drug delivery to the brain.
Objectives: A drug delivery system based on colloidal pegylated gold nanoparticles (PEGAuNPs) conjugated with the tyrosine kinase inhibitor afatinib was designed and tested for enhancing the drug ...activity against pancreatic and NSCLC cells.
Methods: PEGAuNPs were synthesized and characterized physicochemically. Confocal imaging was performed to evaluate the nanoparticle (NP) internalization in cancer cells. For cell-cycle distribution analysis, conjugated NPs and afatinib alone were incubated with cells and alterations on the cell-cycle profile subsequently analyzed by total DNA staining. Cancer cell survival and growth inhibition following incubation with afatinib and PEGAuNPs-afatinib (concentrations between 0.007 and 0.500 µM afatinib) were evaluated.
Results: A higher cellular uptake of PEGAuNPs was observed by cancer cells. Our data suggest an efficient conjugation of PEGAuNPs with the drug, enhancing the afatinib activity in comparison with afatinib alone. In fact, IC
50
and GI
50
results obtained show that the PEGAuNPs-afatinib conjugate is ca. 5 and 20 times more potent than afatinib alone in S2-013 and A549 cell lines, respectively.
Conclusions: Conjugating PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects.
Development of therapeutics for brain disorders is one of the more difficult challenges to be overcome by the scientific community due to the inability of most molecules to cross the blood-brain ...barrier (BBB). Antibody-conjugated nanoparticles are drug carriers that can be used to target encapsulated drugs to the brain endothelial cells and have proven to be very promising. They significantly improve the accumulation of the drug in pathological sites and decrease the undesirable side effect of drugs in healthy tissues. We review the systems that have demonstrated promising results in crossing the BBB through receptor-mediated endocytic mechanisms for the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
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.
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.
A novel system to carry and protect epigallocatechin gallate (EGCG), an antioxidant from the green tea, is reported. The system consists of maltodextrin and gum arabic nanoparticles coated with ...egg-yolk
l-α-phosphatidylcholine (Egg-PC)/stearylamine (SA) bilayers. In this study, the polysaccharide core was produced by homogenization followed by spray-drying. The lipid coating was performed by the lipid film hydration method. The polysaccharide core revealed negative zeta potential, which changed to opposite signs after lipid coating. The presence of lipid layers was evidenced by cryogenic-transmission (cryo-TEM) and scanning (cryo-SEM) electron microscopy studies. An increase in size was observed after lipid coating as determined by dynamic light scattering (DLS). Atomic force microscopy (AFM) demonstrated that the polysaccharide core provides high resistance to mechanical strength. The lipid/particle assemblies show high retention efficiency of EGCG at physiological pH, opening the possibility of their use for delivery and controlled release of tea catechins.
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