Cationic vaccines of nanometric sizes can directly perform the delivery of antigen(s) and immunomodulator(s) to dendritic cells in the lymph nodes. The positively charged nanovaccines are taken up by antigen-presenting cells (APCs) of the lymphatic system often originating the cellular immunological defense required to fight intracellular microbial infections and the proliferation of cancers. Cationic molecules imparting the positive charges to nanovaccines exhibit a dose-dependent toxicity which needs to be systematically addressed.
View Article and Find Full Text PDFGramicidin (Gr) nanoparticles (NPs) and poly (diallyl dimethyl ammonium) chloride (PDDA) water dispersions were characterized and evaluated against Gram-positive and Gram-negative bacteria and fungus. Dynamic light scattering for sizing, zeta potential analysis, polydispersity, and colloidal stability over time characterized Gr NPs/PDDA dispersions, and plating and colony-forming units counting determined their microbicidal activity. Cell viabilities of , , and in the presence of the combinations were reduced by 6, 7, and 7 logs, respectively, at 10 μM Gr/10 μg·mL PDDA, 0.
View Article and Find Full Text PDFAlthough this is an era of pandemics and many devastating diseases, this is also a time when bionanotechnology flourishes, illuminating a multidisciplinary field where vaccines are quickly becoming a balsam and a prevention against insidious plagues. In this work, we tried to gain and also give a deeper understanding on nanovaccines and their way of acting to prevent or cure cancer, infectious diseases, and diseases caused by parasites. Major nanoadjuvants and nanovaccines are temptatively exemplified trying to contextualize our own work and its relative importance to the field.
View Article and Find Full Text PDFSpherical or discoidal lipid polymer nanostructures bearing cationic charges successfully adsorb a variety of oppositely charged antigens (Ag) such as proteins, peptides, nucleic acids, or oligonucleotides. This report provides instructions for the preparation and physical characterization of four different cationic nanostructures able to combine and deliver antigens to the immune system: (1) dioctadecyl dimethylammonium bromide (DODAB) bilayer fragments (DODAB BF); (2) polystyrene sulfate (PSS) nanoparticles (NPs) covered with one cationic dioctadecyl dimethylammonium bromide bilayer (DODAB) named (PSS/DODAB); (3) cationic NPs of biocompatible polymer poly(methyl methacrylate) (PMMA) prepared by emulsion polymerization of the methyl methacrylate (MMA) monomer in the presence of DODAB BF (PMMA/DODAB NPs); (4) antigen NPs (NPs) where the cationic polymer poly(diallyl dimethyl ammonium chloride) (PDDA) directly combined at nontoxic and low dose with the antigen (Ag); when the oppositely charged model antigen is ovalbumin (OVA), NPs are named PDDA/OVA. These nanostructures provide adequate microenvironments for carrying and delivering antigens to the antigen-presenting cells of the immune system.
View Article and Find Full Text PDFNanostructures have been of paramount importance for developing immunoadjuvants. They must be cationic and non-cytotoxic, easily assembling with usually oppositely charged antigens such as proteins, haptens or nucleic acids for use in vaccines. We obtained optimal hybrid nanoparticles (NPs) from the biocompatible polymer poly(methyl methacrylate) (PMMA) and the cationic lipid dioctadecyl dimethyl ammonium bromide (DODAB) by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB.
View Article and Find Full Text PDFAn antimicrobial supramolecular assembly (ASA) is conspicuous in biomedical applications. Among the alternatives to overcome microbial resistance to antibiotics and drugs, ASAs, including antimicrobial peptides (AMPs) and polymers (APs), provide formulations with optimal antimicrobial activity and acceptable toxicity. AMPs and APs have been delivered by a variety of carriers such as nanoparticles, coatings, multilayers, hydrogels, liposomes, nanodisks, lyotropic lipid phases, nanostructured lipid carriers, etc.
View Article and Find Full Text PDFBiocompatible lipid polymer nanoparticles (NPs) previously used as antimicrobial agents are explored here as immuno-adjuvants. Poly (methyl methacrylate) (PMMA)/dioctadecyldimethylammonium bromide (DODAB)/poly (diallyldimethylammonium chloride) (PDDA) nanoparticles (NPs) were prepared by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB and PDDA, with azobisisobutyronitrile (AIBN) as the initiator. NPs characterization after dialysis by dynamic light-scattering yielded 225 ± 2 nm hydrodynamic diameter (Dz), 73 ± 1 mV zeta-potential (), and 0.
View Article and Find Full Text PDFSubunit vaccines rely on adjuvants carrying one or a few molecular antigens from the pathogen in order to guarantee an improved immune response. However, to be effective, the vaccine formulation usually consists of several components: an antigen carrier, the antigen, a stimulator of cellular immunity such as a Toll-like Receptors (TLRs) ligand, and a stimulator of humoral response such as an inflammasome activator. Most antigens are negatively charged and combine well with oppositely charged adjuvants.
View Article and Find Full Text PDFQuaternary ammonium surfactants (QACs) are microbicides, whereas poly (acrylates) are biocompatible polymers. Here, the physical and antimicrobial properties of two QACs, cetyl trimethyl ammonium bromide (CTAB) or dioctadecyl dimethyl ammonium bromide (DODAB) in poly (methyl methacrylate) (PMMA) nanoparticles (NPs) are compared to those of QACs alone. Methyl methacrylate (MMA) polymerization using DODAB or CTAB as emulsifiers and initiator azobisisobutyronitrile (AIBN) yielded cationic, nanometric, homodisperse, and stable NPs.
View Article and Find Full Text PDFBiomimetic nanoparticles are hybrid nanostructures in which the uppermost layer is similar to a cell membrane. In these nanoparticles, lipids and biopolymers can be organized to improve drug incorporation and delivery. This report provides instructions for the preparation and physical characterization of four different biomimetic nanoparticles: (1) polystyrene sulphate (PSS) nanoparticles covered with one cationic dioctadecyl dimethylammonium bromide bilayer (DODAB), which incorporates dimeric channels of the antimicrobial peptide Gramicidin D; (2) silica nanoparticles covered with one single bilayer of the antimicrobial cationic lipid DODAB; (3) hybrid lipid/polymer indomethacin (IND) nanoparticles from injection of IND/DODAB ethanolic solution in a water solution of carboxymethyl cellulose (CMC); (4) bactericidal and fungicidal nanoparticles from DODAB bilayer fragments (BF) covered consecutively by a CMC and a poly(diallyl dimethyl ammonium chloride) (PDDA) layer.
View Article and Find Full Text PDFSince antigens are negatively charged, they combine well with positively charged adjuvants. Here, ovalbumin (OVA) (0.1 mg·mL) and poly (diallyldimethylammonium chloride) (PDDA) (0.
View Article and Find Full Text PDFInt J Mol Sci
December 2019
Hybrid and antimicrobial nanoparticles (NPs) of poly (methyl methacrylate) (PMMA) in the presence of poly (diallyl dimethyl ammonium) chloride (PDDA) were previously obtained by emulsion polymerization in absence of surfactant with low conversion. In the presence of amphiphiles such as cetyl trimethyl ammonium bromide (CTAB), dioctadecyl dimethyl ammonium bromide (DODAB) or soybean lecithin, we found that conversion increased substantially. In this work, the effect of the amphiphiles on the NPs core-shell structure and on the antimicrobial activity of the NPs was evaluated.
View Article and Find Full Text PDFHybrid nanoparticles of poly(methylmethacrylate) synthesized in the presence of poly (diallyldimethyl ammonium) chloride by emulsion polymerization exhibited good colloidal stability, physical properties, and antimicrobial activity but their synthesis yielded poor conversion. Here we create antimicrobial coatings from casting and drying of the nanoparticles dispersions onto model surfaces such as those of silicon wafers, glass coverslips, or polystyrene sheets and optimize conversion using additional stabilizers such as cetyltrimethyl ammonium bromide, dioctadecyldimethyl ammonium bromide, or soybean lecithin during nanoparticles synthesis. Methodology included dynamic light scattering, determination of wettability, ellipsometry of spin-coated films, scanning electron microscopy, and determination of colony forming unities (log CFU/mL) of bacteria after 1 h interaction with the coatings.
View Article and Find Full Text PDFPromiscuous inhibition due to aggregate formation has been recognized as a major concern in drug discovery campaigns. Here, we report some aggregators identified in a virtual screening (VS) protocol to search for inhibitors of human -5'-nucleotidase (-5'-NT/CD73), a promising target for several diseases and pathophysiological events, including cancer, inflammation and autoimmune diseases. Four compounds (, , and ), selected from the ZINC-11 database, showed IC values in the micromolar range, being at the same time computationally predicted as potential aggregators.
View Article and Find Full Text PDFNanotechnology came to stay improving the quality of human life by reducing environmental contamination of earth and water with pathogens. This review discusses how self-assembled antimicrobial nanomaterials can contribute to maintain humans, their water and their environment inside safe boundaries to human life even though some of these nanomaterials display an overt toxicity. At the core of their strategic use, the self-assembled antimicrobial nanomaterials exhibit optimal and biomimetic organization leading to activity at low doses of their toxic components.
View Article and Find Full Text PDFSodium alginate (Alg) reacted with antibiotic gentamicin sulfate (GS) in an aqueous-phase condition mediated by carbodiimide chemistry, in the molar ratios Alg: GS of (1:0.5), (1:1) and (1:2). The Alg-GS conjugated derivatives were characterized by elemental analysis for nitrogen content, Fourier transform infrared spectroscopy in the attenuated total reflection mode (FTIR-ATR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analyses (TGA) and water sorption measurements.
View Article and Find Full Text PDFBackground: Several cationic polymers exhibit a useful antimicrobial property, however the structure-activity relationship still requires a more complete investigation. The main objective of this work is the comparison between the antimicrobial activity and toxicity of free and immobilized poly (diallyldimethylammonium) chloride (PDDA) in biocompatible poly (methylmethacrylate) (PMMA) nanoparticles (NPs).
Results: NPs synthesis by emulsion polymerization is performed over a range of [PDDA] at two methylmethacrylate (MMA) concentrations.
The growing challenge of antimicrobial resistance to antibiotics requires novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes are tested against four multidrug-resistant (MDR) strains of clinical importance. The non-hemolytic poly(diallyldimethylammonium) chloride (PDDA) polymer as the outer NP layer shows a remarkable activity against these organisms.
View Article and Find Full Text PDFPeptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
October 2013
Poly(ethylene glycol), PEG, decorated polystyrene (PS) nanoparticles were synthesized and characterized by means of dynamic light scattering (DLS), zeta (ζ) potential measurements, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The adsorption of Congo red (CR) onto PS/PEG particles was evidenced by the decrease of ζ potential values and increase in the particles mean diameter in comparison to bare particles. Cholesterol oxidase (ChOx), the main enzyme in the oxidation of cholesterol, adsorbed onto PS/PEG and PS/PEG/CR particles, as revealed by the increase in the particles mean size and spectrophotometry.
View Article and Find Full Text PDFCationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs).
View Article and Find Full Text PDFThe present study investigated the effects of ΔΨ and ΔpH (pH gradient) on the interaction of cytochrome c with a mitochondrial mimetic membrane composed of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) leading to vesicle fusion. ΔpH generated by lowered bulk pH (pH(out)) of PCPECL liposomes, with an internal pH (pH(in)) of 8.0, favored vesicle fusion with a titration sigmoidal profile (pK(a) ~ 6.
View Article and Find Full Text PDFMethods Mol Biol
November 2012
Biomimetic nanoparticles are hybrid nanostructures in which the uppermost layer is similar to a cell membrane. This report provides instructions for the preparation and physical characterization of three different types of biomimetic nanoparticles: (1) polystyrene sulfate nanoparticles covered with one cationic dioctadecyldimethylammonium bilayer; (2) silica nanoparticles covered with one neutral phosphatidylcholine bilayer; (3) miconazole particles covered with one anionic dihexadecylphosphate (DHP) bilayer. These examples provide the basis for the preparation and characterization of novel nanoparticles from hydrophobic or hydrophilic and organic or inorganic nanoparticle cores covered with functional outer layers.
View Article and Find Full Text PDFInt J Nanomedicine
April 2010
Mimicking nature is a powerful approach for developing novel lipid-based devices for drug and vaccine delivery. In this review, biomimetic assemblies based on natural or synthetic lipids by themselves or associated to silica, latex or drug particles will be discussed. In water, self-assembly of lipid molecules into supramolecular structures is fairly well understood.
View Article and Find Full Text PDFCytochrome c exhibits two positively charged sites: site A containing lysine residues with high pKa values and site L containing ionizable groups with pKaobs values around 7.0. This protein feature implies that cytochrome c can participate in the fusion of mitochondria and have its detachment from the inner membrane regulated by cell acidosis and alkalosis.
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