Inorganically modified diatomite as a potential prolonged-release drug carrier

Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH 6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (similar to 250 mg/g in 2 h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8 h from both DAMD comprimates (18% after 8 h) and PMDMD comprimates (45% after 8 h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process

Safe-by-design gelatin-modified zinc oxide nanoparticles

We report an innovative low-cost wet precipitation synthesis method for gelatin-modified zinc oxide nanoparticles (GM ZnO NPs) at the interface between the gelatin hydrogel and aqueous electrolyte. Diffusion of ammonia through the hydrogel matrices with different gelatin contents induced precipitation of the product in contact with the surface of the aqueous solution of zinc ions. The obtained precipitate was subjected to thermal treatment to partially decompose the adsorbed gelatin in the NP structure. Physicochemical properties of obtained GM ZnO NPs were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), thermogravimetry (TG), photon correlation spectroscopy (PCS), zeta potential measurements, and inductively coupled plasma-mass spectrometry (ICP-MS). The estimated mean crystallite size of GM ZnO NP powders was in the range from 5.8 to 12.1 nm. The synthesized NPs exhibited nanosheet morphology and arranged into flake-like aggregates. The toxic potential was investigated in vitro in human hepatocellular carcinoma cell line HepG2. The thiazolyl blue tetrazolium bromide (MTS) assay was used to assess cell viability, 2 ',7 '-dichlor-fluorescein-diacetate (DCFH-DA) assay to examine the formation of intracellular reactive oxygen species (ROS), and comet assay to evaluate the genotoxic response. GM ZnO NPs slightly reduced HepG2 cell viability, did not induce ROS formation, and showed low genotoxic potential at very high doses (100 mu g mL(-1)). ZnO NPs fabricated and modified using the proposed methodology deserve further study as potential candidates for antibacterial agents or dietary supplements with low overall toxicity

Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances

With the aid of experimental design, we developed and characterized nanoemulsions for parenteral drug delivery. Formulations containing a mixture of medium-chain triglycerides and soybean oil as oil phase, lecithin (soybean/egg) and polysorbate 80 as emulsifiers, and 0.1M phosphate buffer solution (pH 8) as aqueous phase were prepared by cold high-pressure homogenization. To study the effects of the oil content, lecithin type, and the presence of diazepam as a model drug and their interactions on physicochemical characteristics of nanoemulsions, a three factor two-level full factorial design was applied. The nanoemulsions were evaluated concerning droplet size and size distribution, surface charge, viscosity, morphology, drug-excipient interactions, and physical stability. The characterization revealed the small spherical droplets in the range 195-220nm with polydispersity index below 0.15 and zeta potential between -30 and -60mV. Interactions among the investigated factors, rather than factors alone, were shown to more profoundly affect nanoemulsion characteristics. In vivo pharmacokinetic study of selected diazepam nanoemulsions with different oil content (20%, 30%, and 40%, w/w) demonstrated fast and intense initial distribution into rat brain of diazepam from nanoemulsions with 20% and 30% (w/w) oil content, suggesting their applicability in urgent situations