Raul-Augustin Mitran

Azobenzene functionalized mesoporous AlMCM-41-type support for drug release applications

AbstractA light-responsive material, aminoazobenzene functionalized AlMCM-41, was synthesized and characterized in order to be used as carrier for drug delivery devices. The light-induced hydrophobic-hydrophilic switching effect of azobenzene functionalized aluminosilicate was exploited in the release of irinotecan, a cytostatic drug. To obtain the functionalized mesoporous support, an azobenzene-silane precursor was synthesized by coupling 4-(4′-aminophenylazo) benzoic acid with 3-aminopropyl triethoxysilane and further grafted on AlMCM-41. The azobenzene functionalized mesoporous aluminosilicate exhibited no significant toxicity towards murine fibroblast healthy cells and a reduced toxicity towards murine melanocyte cells. The hybrid materials obtained by loading irinotecan on AlMCM-41 (wt. 35.4%) and aminoazobenzene modified AlMCM-41 (wt. 22%), respectively were characterized by FTIR, small and wide angle XRD, N2 adsorption-desorption isotherms and DSC analyses. A two-fold increase in the drug release rate from azobenzene functionalized aluminosilicate in phosphate buffer solution under UV irradiation was noticed, as compared with dark conditions. Moreover, the azobenzene functionalization of AlMCM-41 significantly increased the irinotecan delivery rate and total cumulative release in comparison with the pristine AlMCM-41 in similar conditions.

Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems

Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development.

Tailoring the dissolution rate enhancement of aminoglutethimide by functionalization of MCM-41 silica: a hydrogen bonding propensity approach

The adsorption and in vitro release properties of the poorly soluble cytostatic agent DL-aminoglutethimide (AGT) on pristine MCM-41, 3-aminopropyl and a novel N-propyl-2-sulfanylacetamide functionalized MCM-41 material were studied. The mesostructured supports and hybrid samples were characterized by small- and wide-angle X-ray diffraction, FT-IR spectroscopy, thermogravimetric and calorimetric analyses, SEM-EDX and N2 adsorption–desorption isotherms. The drug uptake was found to be strongly influenced by its ionization state and solution pH. Drug release experiments show a spectacular increase in the dissolution rate of the therapeutic agent for all hybrid samples, indicating that aminoglutethimide encapsulation into the mesopores of MCM-41-type supports is a viable strategy for dissolution rate enhancement. Using a knowledge-based logit hydrogen bonding propensity model to assess the relative strengths of drug–support supramolecular interactions, we have proposed that a Si–OH⋯Cl− AGT+ mechanism is responsible for the increased drug adsorption in acid media and release rate enhancement at physiological pH.

Controlling drug release from mesoporous silica through an amorphous, nanoconfined 1-tetradecanol layer

Graphical abstract Figure. No caption available. &NA; Mesoporous silica materials are promising nano‐carriers for drug delivery systems. Even though there are many strategies for controlling the drug release kinetics, these must be adapted through trial and error on a case‐by‐case basis. Here we explore the possibility of tailoring the release kinetics of hydrophilic, water soluble therapeutic agents from mesoporous silica through addition of a hydrophobic excipient, 1‐tetradecanol. In vitro drug release experiments performed at 37 °C, in phosphate buffer solution (pH 7.4) show that the addition of tetradecanol yields slower drug release kinetics, which was correlated with the presence of a liquid fatty alcohol interfacial layer. The layer mass is 11–23 wt.% of the metoprolol‐loaded silica sample, and it causes up to 1.6 times decrease of initial release rate with respect to materials without the fatty alcohol. This effect does not depend of carrier pore arrangement, being noticed for both hexagonal MCM‐41 and cubic KIT‐5 mesoporous silica. The toxicity of tetradecanol‐containing materials was evaluated by formazan‐based viability assay on Opossum kidney epithelial cell line, and no significant toxicity was observed.

Effect of Aluminum Incorporation into Mesoporous Aluminosilicate Framework on Drug Release Kinetics

Mesoporous silica materials are promising nanocarriers for the development of drug delivery systems. In this study, the influence of pore size, volume, surface area, and doping the silica framework on the release kinetics of a model drug, metoprolol, has been studied. 20% or 50% wt. therapeutic agent was loaded into the carrier mesopores through incipient wetness impregnation. The carriers and drug-loaded samples have been characterized by small- and wide-angle X-ray diffraction, FT-IR spectroscopy, scanning electron microscopy, and nitrogen adsorption-desorption isotherms. The in vitro release profiles have been fitted using a three-parameter kinetic model and they have been explained in terms of the release rate during the burst and sustained release stages and the fraction of drug molecules released during the burst stage. The silica framework doping with aluminum was found to decrease the amount of drug released in the burst stage, without affecting the other kinetic parameters. The therapeutic agent release rates depend mainly on the pore size and volume of the mesoporous carriers and drug-loaded samples.

Bringing new life into old drugs: a case study on nifuroxazide polymorphism

This paper describes the rational search for and the synthesis of eight new polymorphs, solvates or hydrates of the well-known drug nifuroxazide. By selecting the appropriate polymorph, a 50% increase in solubility was obtained, compared to the commercially available solid form. The target molecule was chosen using hydrogen bond propensity models as a rational approach. All new forms were characterized by X-ray powder diffraction and thermal methods, and, in three cases, by single crystal X-ray diffraction. Two new solid anhydrous polymorphs were discovered and showed a significant increase in solubility and dissolution rates in water over the known solid form.