Description of Release Process of Doxorubicin from Modified Carbon Nanotubes.

The article discusses the release process of doxorubicin hydrochloride (DOX) from multi-wall carbon nanotubes (MWCNTs). The studies described a probable mechanism of release and actions between the surface of functionalized MWCNTs and anticancer drugs. The surface of carbon nanotubes (CNTs) has been modified via treatment in nitric acid to optimize the adsorption and release process. The modification efficiency and physicochemical properties of the MWCNTs+DOX system were analyzed by using SEM, TEM, EDS, FTIR, Raman Spectroscopy and UV-Vis methods. Based on computer simulations at pH 7.4 and the experiment at pH 5.4, the kinetics and the mechanism of DOX release from MWNT were discussed. It has been experimentally observed that the acidic pH (5.4) is appropriate for the efficient release of the drug from CNTs. It was noted that under acidic pH conditions, which is typical for the tumour microenvironment almost 90% of the drug was released in a relatively short time. The kinetics models based on different mathematical functions were used to describe the release mechanism of drugs from MWCNTs. Our studies indicated that the best fit of experimental kinetic curves of release has been observed for the Power-law model and the fitted parameters suggest that the drug release mechanism of DOX from MWCNTs is controlled by Fickian diffusion. Molecular dynamics simulations, on the other hand, have shown that in a neutral pH solution, which is close to the blood pH, the release process does not occur keeping the aggregation level constant. The presented studies have shown that MWCNTs are promising carriers of anticancer drugs that, depending on the surface modification, can exhibit different adsorption mechanisms and release.

Boron and Gadolinium Loaded Fe3O4 Nanocarriers for Potential Application in Neutron Capture Therapy.

In this article, a novel method of simultaneous carborane- and gadolinium-containing compounds as efficient agents for neutron capture therapy (NCT) delivery via magnetic nanocarriers is presented. The presence of both Gd and B increases the efficiency of NCT and using nanocarriers enhances selectivity. These factors make NCT not only efficient, but also safe. Superparamagnetic Fe3O4 nanoparticles were treated with silane and then the polyelectrolytic layer was formed for further immobilization of NCT agents. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), ultraviolet-visible (UV-Vis) and Mössbauer spectroscopies, dynamic light scattering (DLS), scanning electron microscopy (SEM), vibrating-sample magnetometry (VSM) were applied for the characterization of the chemical and element composition, structure, morphology and magnetic properties of nanocarriers. The cytotoxicity effect was evaluated on different cell lines: BxPC-3, PC-3 MCF-7, HepG2 and L929, human skin fibroblasts as normal cells. average size of nanoparticles is 110 nm; magnetization at 1T and coercivity is 43.1 emu/g and 8.1, respectively; the amount of B is 0.077 mg/g and the amount of Gd is 0.632 mg/g. Successful immobilization of NCT agents, their low cytotoxicity against normal cells and selective cytotoxicity against cancer cells as well as the superparamagnetic properties of nanocarriers were confirmed by analyses above.

Kinetic and Equilibrium Studies of Doxorubicin Adsorption onto Carbon Nanotubes.

This study provides deep insight into the adsorption process of doxorubicin onto different types of carbon nanotubes that have been proved to show attractive properties as a drug delivery system. The main aim of the work was to propose probable adsorption mechanisms and interactions between the anticancer drug and surface of modified and pristine carbon nanotubes at blood pH. The carbon nanotubes were oxidized to optimize the absorbance efficiency relative to that of pristine multiwalled carbon nanotubes. The adsorption isotherm of the modified system was well described by the Temkin equation. It confirms that the adsorption in the system studied involves also hydrogen and covalent bonding and is exothermic in nature. The experimental kinetic curves of adsorption were fitted to different mathematical models to check if the kinetics of doxorubicin adsorption onto the modified multiwalled carbon nanotubes follows a pseudo-second-order model and the chemical sorption is bound to be the rate-limiting. On the basis of the molecular dynamics simulation, it was shown that in vacuo the aggregation tendency of doxorubicin molecules is far more favorable than their adsorption on pristine carbon nanotubes (CNTs). It suggests that only functionalization of the nanotube surface can affect the interaction between doxorubicin and functional groups of the carriers and increases the efficiency of the drug loading process.

Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding.

A review of selected literature data related to intramolecular hydrogen bonding in ortho-hydroxyaryl Schiff bases, ortho-hydroxyaryl ketones, ortho-hydroxyaryl amides, proton sponges and ortho-hydroxyaryl Mannich bases is presented. The paper reports on the application of experimental spectroscopic measurements (IR and NMR) and quantum-mechanical calculations for investigations of the proton transfer processes, the potential energy curves, tautomeric equilibrium, aromaticity etc. Finally, the equilibrium between the intra- and inter-molecular hydrogen bonds in amides is discussed.

Carbon fibres as potential bone implants with controlled doxorubicin release.

This work presents the structural characterisation of carbon fibres obtained from the carbonization of flax tow at 400°C (CFs400°C) and 1000°C (CFs1000°C) and the thermodynamic and kinetic studies of adsorption of Doxorubicin (Dox) on the fibres. The characteristic of carbon fibres and their drug adsorption and removal mechanism were investigated and compared with that of natural flax tow. All fibres were fully characterized by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), specific surface area analysis and Boehm titration. The results demonstrated the highest adsorption properties of CFs400°C at 323 K (qmax = 275 mg g-1). The kinetic data followed the pseudo-second-order kinetic model more closely, whereas the Dubinin-Radushkevich model suitably described isotherms for all fibres. Calculated parameters revealed that the adsorption process of Dox ions is spontaneous and mainly followed by physisorption and a pore-filling mechanism. The removal efficiency for carbon fibres is low due to the effect of pore-blocking and hydrophobic hydration. However, presented fibres can be treated with a base for further chemical surface modification, increasing the adsorption capacity and controlling the release tendency.

Vibrational dynamics of ethosuximide polymorphs. Infrared absorption and inelastic neutron scattering spectroscopy and model calculations.

Commercially available and administered to the patients ethosuximide is a racemic mixture of two enantiomers, each of them exist in different conformations. The presence of the species mentioned are proven by the title experimental methods aided by DFT model calculations. Results of the latter are matched against spectroscopic data by the clustering window analysis. One type of hydrogen bonds exist in the solid forms of ethosuximide NH⋯O, leading to the polymorphic variety of the substance studied.

In search of the mutual relationship between the structure, solid-state spectroscopy and molecular dynamics in selected calcium channel blockers.

Three isostructural 1,4-dihydropyridines (DHPs), namely, nifedipine, nitrendipine and nimodipine were selected to characterize their structure, intermolecular interactions and molecular dynamics. The studied samples were analyzed using powder X-ray diffraction (XRD), neutron (INS) and infrared spectroscopy (FT-IR) as well as solid-state nuclear magnetic resonance (NMR), where each technique was supported by the state-of-the-art theoretical calculations for solid-state. By combining multiple experimental techniques with advanced theoretical calculations we were able to shed light on the mutual relation between the structure, stabilizing intermolecular interactions and their spectral response. For the first time, unambiguous computationally-supported assignment of the most prominent spectral features in DHPs is presented to give a valuable support for polymorph screening and drug control. Molecular motions were interpreted in details, revealing that a dynamic reservoir of each compound is dominated by intra-molecular reorientations of methyl groups and large-amplitude oscillations in terminal chains. Our study successfully validates the realm of applicability of first-principles solid-state calculations in search of the mutual relation between the structure and spectroscopy in this important class of drugs. Such approach gives a first necessary step to gather combined structure-dynamics data on functionalized DHPs, which are of importance to better understand crystallization and binding tendency. The NMR relaxation experiments reveal that nitro groups significantly hinder the reorientation of methyl rotors and provide the first evidence of low-temperature methyl-group tunneling in DHPs, an intriguing quantum-effect which is to be further explored.

Calorimetric, FTIR and 1H NMR measurements in combination with DFT calculations for monitoring solid-state changes of dynamics of sibutramine hydrochloride.

Two forms of sibutramine hydrochloride, monohydrate and anhydrous, have been investigated by calorimetric methods, Fourier transform infrared (FTIR) absorption and (1) H nuclear magnetic resonance (NMR) measurements as well as by density functional theory (DFT) of vibrational frequencies and infrared intensities, calculations of steric hindrances and Monte Carlo simulations. The results of FTIR spectra combined with DFT calculations permitted identification of the bands corresponding to the dynamics and vibrations of water molecules. NMR study and Monte Carlo simulations revealed the occurrence of reorientation jumps of the methyl groups in sibutramine cation and also revealed that the reorientation of isopropyl group is possible only in sibutramine monohydrate hydrochloride. The hydration of sibutramine hydrochloride causes a change in the conformation of sibutramine cation.