ABSTRACT
Betulin and its esters are the natural compounds with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of these compounds has limited their applications. We prepared new composites of betulin esters using two methods, namely ball-milling of the mixtures of betulin esters with arabinogalactan and preparation of thin films of these mixtures by evaporating the aqueous solutions. These composites revealed higher water solubility as compared with the initial substances without losing the structural integrity and functionality. As a result, the new composites have shown much higher inhibitory effects against different cancer cell lines such as Ehrlich ascites carcinoma cells and lung carcinoma cells (A549) in comparison with the initial substances. The cell viability studies based on Annexin V and Propidium iodide probes have confirmed the high proapoptotic effect of betulin ester derivatives against cancer cells.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Galactans/chemistry , Triterpenes/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor/methods , Esters/chemistry , Galactans/pharmacology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Microscopy, Electron, Scanning , Solubility , Triterpenes/pharmacologyABSTRACT
A model is proposed which describes the solubilization of a poorly soluble drug in the presence of an insoluble excipient which forms an easily soluble compound with the drug. For sulfathiazole-calcium carbonate system as an example, it is demonstrated using sulfathiazole single crystals and powdered samples that the presence of insoluble additive causes an increase in dissolution rate and solubility of the drug.
Subject(s)
Excipients , Solubility , Calcium Carbonate/administration & dosage , Powders , Sulfathiazole , Sulfathiazoles/chemistryABSTRACT
The anisotropy of structural distortion of the monoclinic polymorph of acetaminophen induced by hydrostatic pressure up to 4.0 GPa was studied by single-crystal X-ray diffraction in a Merrill-Bassett diamond anvil cell (DAC). The space group (P2(1)/n) and the general structural pattern remained unchanged with pressure. Despite the overall decrease in the molar volume with pressure, the structure expanded in particular crystallographic directions. One of the linear cell parameters (c) passed through a minimum as the pressure increased. The intramolecular bond lengths changed only slightly with pressure, but the changes in the dihedral and torsion angles were very large. The compressibility of the intermolecular hydrogen bonds NH...O and OH...O was measured. NH...O bonds were shown to be slightly more compressible than OH...O bonds. The anisotropy of structural distortion was analysed in detail in relation to the pressure-induced changes in the molecular conformations, to the compression of the hydrogen-bond network, and to the changes in the orientation of molecules with respect to each other in the pleated sheets in the structure. Dirichlet domains were calculated in order to analyse the relative shifts of the centroids of the hydrogen-bonded cycles and of the centroids of the benzene rings with pressure.
Subject(s)
Acetaminophen/chemistry , Hydrostatic Pressure , Benzene/chemistry , Crystallization , Crystallography, X-Ray , Hydrogen Bonding , Models, Molecular , Molecular ConformationABSTRACT
Topochemistry of the initial stages of dissolution of monoclinic single crystals of acetaminophen was studied. Etching pits were identified with the sites of emerging dislocations. Etching of different faces with a solution of ethyl acetate in carbon tetrachloride gave different shapes of etching pits. An interpretation of this result was suggested, based on the analysis of the anisotropy of the crystal structure. Etching of the same crystal face with different etching agents was shown to result in different shapes of etching pits.
