The new concepts of personalized and precision medicine require the design of more and more refined delivery systems. In this frame, hydrogels can play a very important role as they represent the ...best surrogate of soft living tissues for what concerns rheological properties. Thus, this paper focusses on a global theoretical approach able to describe how hydrogel polymeric networks can affect the release kinetics of drugs characterized by different sizes. The attention is focused on a case study dealing with an interpenetrated hydrogel made up by alginate and poly(
-vinyl-2-pyrrolidone).
Information about polymeric network characteristics (mesh size distribution and polymer volume fraction) is deduced from the theoretical interpretation of the rheological and the low field Nuclear Magnetic Resonance (NMR) characterization of hydrogels. This information is then, embodied in the mass balance equation whose resolution provides the release kinetics.
Our simulations indicate the influence of network characteristics on release kinetics. In addition, the reliability of the proposed approach is supported by the comparison of the model outcome with experimental release data.
This study underlines the necessity of a global theoretical approach in order to design reliable delivery systems based on hydrogels.
Anomerization of simple sugars in the liquid phase is known as an acid- and base-catalyzed process, which highly depends on solvent polarity. This reaction is reported here to occur in the gas phase, ...during traveling wave ion mobility spectrometry (TWIMS) experiments aimed at separating α- and β-anomers of penta-acrylated glucose generated as ammonium adducts in electrospray ionization. This compound was available in two samples prepared from glucose dissolved in solvents of different polarity, namely tetrahydrofuran (THF) and
N,N
-dimethylacetamide (DMAC), and analyzed by electrospray tandem mass spectrometry (ESI-MS/MS) as well as traveling wave ion mobility (ESI-TWIMS-MS). In MS/MS, an anchimerically-assisted process was found to be unique to the electrosprayed α-anomer, and was only observed for the THF sample. In ESI-TWIMS-MS, a signal was measured at the drift time expected for the α-anomer for both the THF and DMAC samples, in apparent contradiction to the MS/MS results, which indicated that the α-anomer was not present in the DMAC sample. However, MS/MS experiments performed after TWIMS separation revealed that ammonium adducts of the α-anomer produced from each sample, although exhibiting the same collision cross section, were clearly different. Indeed, while the α-anomer actually present in the THF sample was electrosprayed with the ammonium adducted at the C2 acrylate, its homologue only observed when the DMAC sample was subjected to TWIMS hold the adducted ammonium at the C1 acrylate. These findings were explained by a β/α inter-conversion upon injection in the TWIMS cell, as supported by theoretical calculation and dynamic molecular modeling.
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Practically, all photoswitchable catalysts exhibit residual activity in the OFF state. Herein, we present a ruthenium initiator with a built-in photoswitch whose metathetical performance is ...completely shut off by light. The system is made of Hoveyda–Grubbs second-generation complexes appended, along with background ligands, to a gold nanoparticle surface via azobenzene linkers. Under dark or visible lightthe precatalysts, in the presence of an olefin, undergo initiation, diffuse from the surface into bulk solution, and commence metathesis reaction. When the conditions are changed to ultraviolet, the isomerization of the azo switches takes place, burying the precatalysts within the bulky organic monolayer, thus preventing their initiation and thereby halting the reaction. Despite the irreversibility of the process, this work opens up opportunities for the remote deactivation of catalysts without their chemical decomposition and control of more complex tasks such as chemical selectivity.
The sensing of small molecules poses the challenge of developing devices able to discriminate between compounds that may be structurally very similar. Here, attention has been paid to the use of ...self-assembled monolayer (SAM)-protected gold nanoparticles since they enable a modular approach to tune single-molecule affinity and selectivity simply by changing functional moieties (i.e., covering ligands), along with multivalent molecular recognition. To date, the discovery of monolayers suitable for a specific molecular target has relied on trial-and-error approaches, with ligand chemistry being the main criterion used to modulate selectivity and sensitivity. By using molecular dynamics, we showcase that either individual molecular characteristics and/or collective features such as ligand flexibility, monolayer organization, ligand local ordering, and interfacial solvent properties can also be exploited conveniently. The knowledge of the molecular mechanisms that drive the recognition of small molecules on SAM-covered nanoparticles will critically expand our ability to manipulate and control such supramolecular systems.
Schematic representation of possible covalent bonds formation between the Si atoms of the aminosilane and the MMT surface O atoms.
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► The degree of silylation of Na-MMT increases with ...increasing the length of the aminosilane organic moieties, the overall aminosilane concentration, and temperature. ► Higher temperature and aminosilane concentration values lead to an increased amount of chemically bonded silanes with respect to the intercalated species. ► The longer the organic chain on the aminosilane molecules, the smaller the
d-spacing in the relevant modified MMT.
In this work, the silylation of sodium montmorillonite (Na-MMT) was performed in glycerol using 3-aminopropyltriethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane and 3-2-(2-aminoethylamino)ethylamino-propyl-trimethoxysilane. The effects on the
d-spacing of sodium montmorillonite (Na-MMT) upon reaction with three aminosilanes of different chain length were studied in details by combining experimental and computational techniques. Infrared spectroscopy was used to monitor the grafting process, while the degree of grafting was calculated using thermogravimetric analysis. X-ray diffraction experiments were carried out to evaluate the shift of the (0
0
1) basal spacing. It was found that the degree of silylation of Na-MMT increases with increasing the length of the aminosilane organic moieties, the overall aminosilane concentration, and temperature. The same beneficial effects were observed on the silicate
d-spacing, as its value increases with increasing silane concentration and reaction temperature. Remarkably, however, increasing the length of the organic chains in the silane modifiers resulted in decreasing values of the Na-MMT interlayer distance. A rationale for this behavior is proposed on the basis of atomistic molecular dynamics simulation evidences.
The spontaneous self-organization of dissimilar ligands on the surface of metal nanoparticles is a very appealing approach to obtain anisotropic “spherical” systems. In addition to differences in ...ligand length and end groups, a further thermodynamic driving force to control the self-assembled monolayer organization may become available if the ligands are inherently immiscible, as is the case of hydrogenated (H-) and fluorinated (F-) species. Here, we validate the viability of this approach by combining 19F NMR experiments and multiscale molecular simulations on large sets of mixed-monolayer-protected gold nanoparticles (NPs). The phase segregation of blends of F- and H-thiolates grafted on the surface of gold NPs allows a straightforward approach to patterned mixed monolayers, with the shapes of the monolayer domains being encoded in the structure of the F/H-thiolate ligands. The results obtained from this comprehensive study offer molecular design rules to achieve a precise control of inorganic nanoparticles protected by specifically patterned monolayers.
We report the simple synthesis and full investigation of a novel heparin binding dye, mallard blue, an arginine-functionalized thionine. This dye binds heparin in highly competitive media, including ...water with high levels of competitive electrolyte, buffered aqueous solution and human serum. The dye reports on heparin levels by a significant change in its UV–vis spectroscopic profile. Molecular dynamics modeling provides detailed insight into the binding mode. Heparin binding is shown to be selective over other glycosaminoglycans, such as hyaluronic acid and chondroitin sulfate. Importantly, we demonstrate that, in the most competitive conditions, mallard blue outperforms standard dyes used for heparin sensing such as azure A.
In this work we report, compare and discuss the results obtained from fully atomistic molecular dynamics simulations of generations 4, 5, and 6 of PAMAM‐based dendrimers having NH3 and ...triethanolamine as cores, forming complexes with a short interfering RNA (siRNA) at different pH values and at physiological ionic strength. By employing a detailed analysis we demonstrate how features such as molecular size, structural details, and protonation level of this category of dendrimers affect the dendrimer/siRNA complexation. Properties like the conformational flexibility of the dendrimer, the effective charge distribution of the assembly, and the level of intra‐ and intermolecular hydrogen bonding between the two molecular entities are all found to play a significant role in the mutual interactions between the nucleic acid and the hyperbranched molecules. All these features are of key importance in the multifaceted mechanism of dendrimer/gene complexation, and their understanding can provide valuable insight toward the design of more efficient nucleic acid nanocarriers.
Results obtained from molecular dynamics simulations of high‐generation PAMAM‐based dendrimers having NH3 and triethanolamine as cores, forming complexes with a short interfering RNA at different pH values and at physiological ionic strength, are reported. The structural flexibility of the triethanolamine‐core dendrimer allows a higher degree of penetration of the siRNA strands within the dendritic structure resulting in the formation of more stable complexes.
Molecular self-assembly is a topic attracting intense scientific interest. Various strategies have been developed for construction of molecular aggregates with rationally designed properties, ...geometries, and dimensions that promise to provide solutions to both theoretical and practical problems in areas such as drug delivery, medical diagnostics, and biosensors, to name but a few. In this respect, gold nanoparticles covered with self-assembled monolayers presenting nanoscale surface patterns—typically patched, striped or Janus-like domains—represent an emerging field. These systems are particularly intriguing for use in bio-nanotechnology applications, as presence of such monolayers with three-dimensional (3D) morphology provides nanoparticles with surface-dependent properties that, in turn, affect their biological behavior. Comprehensive understanding of the physicochemical interactions occurring at the interface between these versatile nanomaterials and biological systems is therefore crucial to fully exploit their potential. This review aims to explore the current state of development of such patterned, self-assembled monolayer-protected gold nanoparticles, through step-by-step analysis of their conceptual design, synthetic procedures, predicted and determined surface characteristics, interactions with and performance in biological environments, and experimental and computational methods currently employed for their investigation.
siRNA delivery remains a major challenge in RNAi‐based therapy. Here, we report for the first time that an amphiphilic dendrimer is able to self‐assemble into adaptive supramolecular assemblies upon ...interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available nonviral vectors. In addition, this amphiphilic dendrimer is able to harness the advantageous features of both polymer and lipid vectors and hence promotes effective siRNA delivery. Our study demonstrates for the first time that dendrimer‐based adaptive supramolecular assemblies represent novel and versatile means for functional siRNA delivery, heralding a new age of dendrimer‐based self‐assembled drug delivery in biomedical applications.
Vesicle‐like dendrimersomes formed through the self‐assembly of an amphiphilic dendrimer are able to undergo structural rearrangement into spherical micelles to entrap and condense siRNA into stable nanoparticles, which protect siRNA and promote siRNA delivery in various cells, including human primary and stem cells, as well as in vivo. This system combines the advantages of lipid and dendrimer vectors, hence constituting a novel and efficient siRNA delivery platform.
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