Abstract:The interaction of the antibacterial polymer–branched poly(ethylene imine) substituted with quaternary ammonium groups, PEO and alkyl chains, PEI25QI5J5A815–with a solid supported lipid bilayer was investigated using surface sensitive optical waveguide spectroscopy. The analysis of the optogeometrical parameters was extended developing a new composite layer model in which the structural and optical anisotropy of the molecular layers was taken into consideration. Following in situ the change of optical birefrin… Show more
“…The interfacial properties which influence the interactions in biological environments might be conveniently investigated using simplified models of complex cell membranes [21]. The bilayer [22] or lipid monolayer systems are widely used to characterize quantitatively the membrane affinity of bioactive molecules and reveal the resulting structural changes [23][24][25][26][27]. Nevertheless, the interaction of drug delivery NPs with lipid monolayer is rarely investigated although such studies could be effectively used in developing functionalized nanocarrier systems [2,25,28].…”
Biodegradable poly(lactic-co-glycolic acid)(PLGA 50:50) nanoparticles (NPs) were prepared and characterized in terms of size, composition, zeta potential and colloidal stability. Surface modification of PLGA NPs where primary amino groups were introduced to the Pluronic surface layer was developed. This method allows modulation of the charge character of the nanoparticle surface and provides functional groups for chemical reactions useful for targeting while retaining the aggregation stability of the system. The nanoparticles showed significant interaction with model membrane system (DPPC and DPPC+DPPG lipid layers) depending on the amount and type of Pluronic applied for stabilization of NPs. A new antitubercular drug candidate was encapsulated into the PLGA NPs. The cellular uptake and the intracellular efficacy against Mycobacterium tuberculosis (Mtb) of the drug and the drug loaded nanoparticulate systems were investigated. These formulations were successfully taken up by MonoMac6 human monocyte cells and highly enhanced the availability and efficacy of the drug against Mtb which was demonstrated in comparative in vitro experiments.
“…The interfacial properties which influence the interactions in biological environments might be conveniently investigated using simplified models of complex cell membranes [21]. The bilayer [22] or lipid monolayer systems are widely used to characterize quantitatively the membrane affinity of bioactive molecules and reveal the resulting structural changes [23][24][25][26][27]. Nevertheless, the interaction of drug delivery NPs with lipid monolayer is rarely investigated although such studies could be effectively used in developing functionalized nanocarrier systems [2,25,28].…”
Biodegradable poly(lactic-co-glycolic acid)(PLGA 50:50) nanoparticles (NPs) were prepared and characterized in terms of size, composition, zeta potential and colloidal stability. Surface modification of PLGA NPs where primary amino groups were introduced to the Pluronic surface layer was developed. This method allows modulation of the charge character of the nanoparticle surface and provides functional groups for chemical reactions useful for targeting while retaining the aggregation stability of the system. The nanoparticles showed significant interaction with model membrane system (DPPC and DPPC+DPPG lipid layers) depending on the amount and type of Pluronic applied for stabilization of NPs. A new antitubercular drug candidate was encapsulated into the PLGA NPs. The cellular uptake and the intracellular efficacy against Mycobacterium tuberculosis (Mtb) of the drug and the drug loaded nanoparticulate systems were investigated. These formulations were successfully taken up by MonoMac6 human monocyte cells and highly enhanced the availability and efficacy of the drug against Mtb which was demonstrated in comparative in vitro experiments.
“…Such lysis can be achieved more directly with polymers that have both cationic and hydrophobic groups and, therefore, have cationic detergent character. 41,42 This latter lysis is not analogous to the polymer-induced phage activation of the previous paragraphs. The reasons are that lysis by the cationic detergent-like polymers (1) occurs in biofilms generated by pure bacterial cultures, (2) often occurs "on contact" and (3) occurs via immediate damaging effects on bacterial membranes.…”
Section: Improving the Propagation Of 0305phi8-36 And Other Large Phagesmentioning
confidence: 90%
“…The reasons are that lysis by the cationic detergent-like polymers (1) occurs in biofilms generated by pure bacterial cultures, (2) often occurs "on contact" and (3) occurs via immediate damaging effects on bacterial membranes. 41,42 However, cationic polymer-activation of endogenous phages is still a possible (apparently unexplored) factor in the wild.…”
Section: Improving the Propagation Of 0305phi8-36 And Other Large Phagesmentioning
D rug development has typically been a primary foundation of strategy for systematic, long-range management of pathogenic cells. However, drug development is limited in speed and flexibility when response is needed to changes in pathogenic cells, especially changes that produce drug-resistance. The high replication speed and high diversity of phages are potentially useful for increasing both response speed and response flexibility when changes occur in either drug resistance or other aspects of pathogenic cells. We present strategy, with some empirical details, for (1) using modern molecular biology and biophysics to access these advantages during the phage therapy of bacterial infections, and (2) initiating use of phage capsid-based drug delivery vehicles (DDVs) with procedures that potentially overcome both drug resistance and other present limitations in the use of DDVs for the therapy of neoplasms. The discussion of phage therapy includes (a) historical considerations, (b) changes that appear to be needed in clinical tests if use of phage therapy is to be expanded, (c) recent work on novel phages and its potential use for expanding the capabilities of phage therapy and (d) an outline for a strategy that encompasses both theory and practice for expanding the applications of phage therapy. The discussion of DDVs starts by reviewing current work on DDVs, including work on both liposomal and viral DDVs. The discussion concludes with some details of the potential use of permeability constrained phage capsids as DDVs.
“…Uniaxial birefringence is characteristic for layers formed by intra-molecular anisotropic species, such as surfactants [58] and proteins with domain organisation [59]. If it is assumed that the individual mucin molecules are too unstructured to be intra-molecularly anisotropic, such as is the case with surfactant molecules, the observed uniaxial birefringence must originate from asymmetry of the adsorbed layer.…”
Section: Adsorbate Anisotropy Revealed By Adlayer Birefringencementioning
The kinetic adsorption-desorption behaviour of porcine gastric mucin in the presence of physiologically relevant concentrations of the polyphenol epigallocatechin gallate (EGCG) was investigated using high-resolution kinetic optical waveguide lightmode spectroscopy (OWLS) and atomic force microscopy (AFM). Comparison with dynamic light scattering results from EGCGmucin mixtures indicates that discrete particles are formed whose size increases with increasing EGCG:mucin ratio. These particles are deduced to be the adsorbing entities, which fuse on the surface to form complex surface layers. At low molar EGCG:mucin ratios (< 1000), aggregates fuse on the surface to form a monolayer similar to one of pure mucin. With increasing EGCG concentration, the surface assembly of aggregates becomes consistent with their rearrangement and spreading in the shape of a spherical segment. At the highest molar ratios investigated (> 12 000) the particles begin to destabilize. The presence of EGCG leads to birefringence hysteresis during adsorption-desorption, indicating structural rearrangement, even at molar ratios 1000. The intensification of the phenomenon with increasing EGCG:mucin ratio mimics what was previously observed with the increase of mucin concentration in an EGCG-free system.
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