Silver Is Not Equal to Silver: Synthesis and Evaluation of Silver Nanoparticles with Low Biological Activity, and Their Incorporation into C12Alanine-Based Hydrogel.

A new type of silver nanoparticles (AgNPs) was prepared and comprehensively studied. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses indicated that 24 nm AgNPs with narrow size distribution were obtained while Z-potential confirms their good stability. The composites of the obtained AgNPs with nontoxic-nature-inspired hydrogel were formed upon cooling of the aqueous solution AgNPs and C12Ala. The thermal gravimetric analysis (TGA) and the differential scanning calorimetry (DSC) do not show significant shifts in the characteristic temperature peaks for pure and silver-enriched gels, which indicates that AgNPs do not strongly interact with C12Ala fibers, which was also confirmed by SEM. Both AgNPs alone and in the assembly with the gelator C12Ala were almost biologically passive against bacteria, fungus, cancer, and nontumor human cells, as well as zebra-fish embryos. These studies proved that the new inactive AgNPs-doped hydrogels have potential for the application in therapy as drug delivery media.

New Supramolecular Drug Carriers: The Study of Organogel Conjugated Gold Nanoparticles.

An aqueous solution of sodium citrate stabilized gold nanoparticles (AuNP) in the presence of N-lauroyl-L-alanine (C12ALA) forms a stable gel. The structure of the gel and the distribution profile of AuNP in it were analyzed. Will nanoparticles separated from each other with sodium citrate behave in the same way in solution and trapped in the gel matrix? Will the spatial limitation of solvent molecules aggregate nanoparticles and destroy their homogeneity? These questions are very important from the point of view of the use of gold nanoparticles, trapped in the gel structure as carriers of drugs in the slow-release process. The lack of homogeneity of this distribution will have a major impact on the rate of release of the appropriate amount of therapeutic drug from the matrix. In this work, we attempt to answer these questions. The performed biological assays revealed that both C12ALA and C12ALA-AuNP show an excellent level of biological neutrality. They might be used as a transporting medium for a drug delivery without affecting the drug's activity.

Effect of gel matrix confinement on the solvent dynamics in supramolecular gels.

Supramolecular gels formed by the sugar gelator of methyl-4,6-O-(p-nitrobenzylidene)-α-d-glucopyranoside (1) with 1,3-propanediol (PG) and 1-butanol (BU) were prepared with different gelator concentrations. The solvent dynamics within gels, characterized by the diffusion coefficient (D) and the spin-lattice relaxation time (T1), was the subject of NMR diffusometry and relaxometry studies. The diffusion was studied as a function of diffusion time and gelator concentrations. The relaxation time was measured as a function of Larmor frequency. The decrease of the diffusion coefficient was observed as a function of diffusion time for both gels and for all studied gelator concentrations. It is indicative of the confinement effect due to the geometrical restrictions of the gel matrix. The relaxation data for PG solvent confined in 1/PG gel revealed the low frequency dispersion (in kHz region) which is a fingerprint of a specific interaction experienced by PG solvents in the presence of the rigid structure of gelator 1 aggregates. The relaxation model, well known from the interpretation of liquid confined in nanopores as reorientations mediated by translational displacements (RMTD), was successfully applied to analyze the data of studied solvents confined in matrices of supramolecular gels. The microstructures of gel matrices were imaged by Polarized Microscopy.

The solvent-gelator interaction as the origin of different diffusivity behavior of diols in gels formed with sugar-based low-molecular-mass gelator.

Organogels are soft materials consisting of low-molecular-mass gelators (LMOGs) self-assembled through noncovalent interactions into 3D structures, in which free spaces are filled by organic solvents. 4,6,4',6'-O-terephthylidene-bis(methyl-α-d-glucopyranoside) (1) is found to be a new LMOG. It gelatinizes only a limited number of solvents. Here, the gels of 1 with ethylene glycol (EG) and 1,3-propanediol (PG) are investigated with FT-IR, Raman, and UV-vis spectroscopies, the NMR relaxometry and diffusometry methods, and microscopic observation. The chemical structures of both solvents are closely related, but the variety of physical characteristics of the gels is large. The 1/PG gels are thermally more stable compared to 1/EG gels. The types of aggregates are most likely the H- and J-type in 1/EG gels and the J-type in 1/PG gels. Different microstructures are observed: bundles of crossing fibers for 1/EG and a honeycomb-like matrix for 1/PG gels. The diffusivity of the EG solvent in gels with 1 behaves as expected, decreasing with increasing gelator concentration, whereas the opposite behavior is observed for the PG solvent. This is a most fascinating result. To explain the diffusion enhancement, we suggest that a dynamic hydrogen bonding network of PG solvent in gel matrixes is disrupted due to solvent-gelator interaction. The direct proof of this interaction is given by the observed low frequency dispersion of the spin-lattice relaxation time of solvents in the gel matrixes.

Diffusive diffraction phenomenon observed by PGSE NMR technique in a sugar-based low-molecular-mass gel.

The paper presents the diffusive diffraction phenomenon observed by the single-pulse-gradient spin-echo (s-PGSE) NMR technique in a real porous material: a gel composed of low-molecular-mass gelator methyl-4,6-O-(p-nitrobenzylidene)-α-D-glucopyranoside and toluene. Thanks to this phenomenon, we can probe the true microstructure (not xerogel) in which the toluene diffuses. To analyze the measured diffusion-diffraction pattern, we employed a composite bicompartmental model that superimposes restricted diffusion in small cavities of the gel matrix within the bundles of crossing fibers, with free diffusion in large and unconfined compartments between the bundles of crossing fibers. For restricted diffusion a pore-hopping formalism was applied. The observation of the diffraction pattern and its analysis leads to the conclusion that the pores, in the slow diffusing compartment of studied gel are ordered, at least locally, and relatively monodisperse with a size of 64 µm. Moreover, the restricting walls formed by the crossing fibers are perpendicular to the direction of the diffusion gradient.

A possible application of magnetic resonance imaging for pharmaceutical research.

Magnetic resonance imaging (MRI) is a non-destructive and non-invasive method, the experiment can be conducted in situ and allows the studying of the sample and the different processes in vitro or in vivo. 1D, 2D or 3D imaging can be undertaken. MRI is nowadays most widely used in medicine as a clinical diagnostic tool, but has still seen limited application in the food and pharmaceutical sciences. The different imaging pulse sequences of MRI allow to image the processes that take place in a wide scale range from ms (dissolution of compact tablets) to hours (hydration of drug delivery systems) for mobile as well as for rigid spins, usually protons. The paper gives examples of MRI application of in vitro imaging of pharmaceutical dosage based on hydroxypropyl methylcellulose which have focused on water-penetration, diffusion, polymer swelling, and drug release, characterized with respect to other physical parameters such as pH and the molecular weight of polymer. Tetracycline hydrochloride was used as a model drug. NMR imaging of density distributions and fast kinetics of the dissolution behavior of compact tablets is presented for paracetamol tablets.

How we can interpret the T1 dispersion of MC, HPMC and HPC polymers above glass temperature?

The chain dynamics in methyl cellulose (MC), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were studied with the aid of field-cycling NMR relaxometry technique in the temperature range from 300 to 480 K that is above the glass transition, but below thermal degradation. The frequency dependence of proton spin-lattice relaxation time was determined between 24 kHz and 40 MHz for selected temperatures. The experimental spin-lattice relaxation dispersion data were fitted with the power law relations of T(1) proportional variant omega(gamma) predicted by the tube/reptation model. The exponent's values found from the fitting procedure for MC, HPMC and HPC almost exactly match the ones predicted in tube/reptation model for limit II (gamma=0.75) and in MC also for limit III (gamma=0.50). Remarkably, this finding concerns the polymers in networks formed of the same polymer species.

Spatially resolved solvent interaction with glassy HPMC polymers studied by magnetic resonance microscopy.

Magnetic resonance microscopy was used to study the interaction of an alkaline water solvent (pH=12) with hydroxypropylmethyl cellulose (HPMC) matrices with different molecular masses Mw=12,000, 86,000, and 120,000. The polymers in the form of cylinders were hydrated at 37 degrees C and monitored at equal time intervals with a 300MHz Bruker AVANCE. The spatially resolved spin-spin relaxations times T2 and diffusion coefficients D of the solvent molecules within the gel layer of HPMC samples, along with changes in the dimension of the glass core of the polymers were determined as a function of hydration times. The experimental data allows us to characterize the diffusion mechanism as being Fickian and to determine the mean diffusivity values D of the solvent molecules for each voxel within the gel of the studied polymers. The influence of the molecular mass of the HPMC polymers on swelling properties has been shown.

The swelling properties of hydroxypropyl methyl cellulose loaded with tetracycline hydrochloride: magnetic resonance imaging study.

Magnetic resonance imaging was used to study the behavior of the gel layer thickness in hydroxypropyl methyl cellulose (HPMC) matrices loaded with different amounts of soluble tetracycline hydrochloride. The time dependence of the diffusion front, effective T2, and proton-density analysis clearly indicates a Case II diffusion mechanism in the system composed of water solution of hydrochloric acid (pH = 2) and HPMC. The solvent penetration front was used to describe the swelling properties as well as the integrity of the HPMC matrices. The results show that the tetracycline hydrochloride decreases the resistance of the HPMC network structure against the movement of solvent molecules. On the other hand the swelling properties of the matrix increase with the amount of drug in the matrix.

Magnetic resonance imaging study of the transport phenomena of solvent into the gel layer of hypromellose matrices containing tetracycline hydrochloride.

Magnetic resonance imaging was used to study the diffusion of a water solution of hydrochloric acid into hypromellose (hydroxypropylmethylcellulose) matrices. Spatially resolved information was obtained about the self-diffusion coefficient and spin-spin relaxation time of solvent protons in the gel layer of hypromellose matrices loaded with different amounts of tetracycline hydrochloride. The data showed the influence of the drug concentration on the diffusion and spin-spin relaxation. Higher drug concentrations in the hypromellose matrix led to greater swelling of the matrix and faster diffusion of the water molecules inside the gel layer of the polymer. The observed differences between the radial and axial diffusion were interpreted in terms of the stresses imposed in the axial direction during the compression of the samples. The spin-spin and diffusion profiles indicated that the diffusion of a water solution of hydrochloric acid into hypromellose, pure and loaded with different amounts of tetracycline hydrochloride, was characterized as a Case II mechanism.

In situ, real time observation of the disintegration of paracetamol tablets in aqueous solution by magnetic resonance imaging.

The disintegration behavior of paracetamol tablets was studied by magnetic resonance imaging (MRI) using the Snapshot FLASH method. The total time of the single experiment is 425 ms and allows the study of the disintegration process in real time. The study was carried out in vitro under acidic gastric pH conditions and may help to predict the behavior of paracetamol tablets in the stomach after oral administration. It was shown that in spite of identical conditions, the disintegration of the tablets under study was different. The distribution of protons of 4-(N-acetyl)aminophenol within the paracetamol tablet was shown to be homogeneous. The study was carried out in a non-destructive way by the SPI MRI method.