Zinc oxide nanoparticles (ZnO NPs) modified by oxopyrymidine alcohol, also known as xymedone (Xym), were obtained and studied using FTIR, UV-vis, and fluorescent spectroscopy, and SEM, BET, powder XRD, and DLS analysis. A formulation of thixotropic hydrophilic gels containing Carbopol-based Xym and ZnO NPs was developed. A vertical Franz cell with a cellulose acetate membrane was used as a model to investigate the passive diffusion of the gel components by AAS. The gel components—Xym and ZnO NPs—were shown to penetrate through acetyl cellulose membrane within 5–7 h depending on an initial amount, and its values were in the range of 56–77%. The penetration of modified ZnO NPs by Xym was more effective in contrast to ZnO NPs without modification. The burn wound healing activity of ZnO NPs–Xym gel was demonstrated on a thermal burn wound model on rats. SOD and GR activity was increased by 30–35% during ZnO NPs–Xym gel treatment, the burn area on 10 postburn day decreased by 10% in contrast to a positive control, Methyluracyl®® ointment.
In this work we studied nanoceria (CeO2NPs) and nanoceria modified by 5-fluorouracil (5FU) as potential APIs. Nanoceria were synthesized by precipitation in a matrix of hydroxyethyl cellulose or hydroxypropylmethyl cellulose, using cerium (III) nitrate and meglumine. Nanoceria properties were estimated by UV, FTIR and X-ray photoelectron spectra; scanning electron and atomic force microscopy; powder X-ray diffraction patterns and energy dispersive X-ray microanalysis. The cytotoxicity of nanoceria and polymer-protected nanoparticles was evaluated using the established cell line NCTC clone 929 (C3H/An mouse, subcutaneous connective tissue, clone of L. line). The morphology and metabolic activity of nanoparticles at 10 μg∙mL−1 of cells was not significant. In addition, the cytotoxic effects of nanoceria were assessed on two human colorectal cancer cell lines (HT29 and HCT116), murine melanoma B16 cells and normal human skin fibroblasts. An inhibitory effect was shown for HCT116 human colorectal cancer cells. The IC50 values for pure CeO2NPs and CeO2NPs-5FU were 219.0 ± 45.6 μg∙mL−1 and 89.2 ± 14.0 μg∙mL−1, respectively. On the other hand, the IC50 of 5FU in the combination of CeO2NPs-5FU was 2-fold higher than that of pure 5FU, amounting to 5.0 nmol∙mL−1. New compositions of nanoceria modified by 5-fluorouracil in a polymer matrix were designed as a dermal polymer film and gel. The permeability of the components was studied using a Franz cell.
Introduction. The review considered the basic concepts of drug release and kinetic modeling of this process from dosage forms (DF) according to the dissolution profile using a vertical Franz diffusion cell. Text. Drug release from dosage forms (ointments, gels, transdermal patches and polymer films) is usually described as the processes of drug dissolution in the biological system. Formally, this process, in accordance with pharmacopoeial methods, is assessed using various solubility tests. The theoretical aspects of drug release are based on the theory of mass transfer of substances from a polymer matrix into a system that simulates a biological environment. Drug release can be carried out via the passive diffusion mechanism according to Fick and "non-Fick" diffusion, drug desorption from the inner side of the membrane, as well as other mechanisms. Drug release is determined both lipophilicity and the membrane nature, both various physicochemical parameters of the drug. One of the correlation characteristics of mass transfer is the assessment of the permeability coefficient for a specific membrane that simulates skin. Permeability coefficient describes the rate of penetration of a drug per unit concentration in distance/time units. An example of relationship of "structure-permeability" correlation are the equations relating the permeability constant and lipophilicity to the molecular weight of the drug. The paper showed statistical methods of data analysis (MANOVA, ANOVA) and model-dependent methods (zero order, first order, Higuchi model, Korsmeyer – Peppas model, Hixson – Crowell model, etc.). The ideal drug delivery of non-degradable and non-disaggregating drugs describes as drug release model by zero-order reaction. For drug release of water-soluble drugs from a porous matrix, first-order reaction model is more typical. Kinetic models of fractional power functions are used usually as the cube root law (Hixson – Crowell model) or the square root law (Higuchi model) to describe the process of drug release from gels and dermal films and patches. The Korsmeyer – Peppas model allows us to evaluate the mechanism of mass transfer with Fickian diffusion or another process. Conclusion. Mathematical modeling of the drug release kinetics from soft dosage forms is an important element for the development and optimization of their compositions. The study of the drugs release from soft dosage forms, including TTS and polymer films, as well as the release from solid dosage forms, is based on establishing correlations between the kinetics of the release and dissolution profile. The main release models, regardless of the DF, remain the following models: zero order, first order, Korsmeyer – Peppas, Higuchi, Hickson – Crowell, the empirical or semi-empirical constants of which vary significantly depending on the DF and the release mechanism (Fickian diffusion or another drug mass transfer mechanism). Correlation relationships QSPeR or QSPR, using the coefficients of permeability, diffusion and lipophilicity, provide information on the mass transfer of drugs through the skin.
In this work the approaches to assess of the xymedone release from hydrophilic gels with zinc oxide nanoparticles were proposed using a vertical Franz diffusion cell at 37 ℃. A partial validation protocol included the varying of the membrane polarity (lipophilic or hydrophilic cellulose acetate), the acceptor chamber volume (4,35 mL or 12,71 mL), the gel composition (with or without zinc oxide nanoparticles), as well as the metrological characteristics for the xymedone assay when it was released through the membrane in a Franz cell. It was estimated that the Franz cell with the volume of 12,71 mL, and the lipophilic membrane made it possible to estimate the amount of xymedone released with less error (RSD no more than 2%). We showed that the xymedone immobilization into zinc oxide nanoparticles increased the efficiency of xymedone release from the hydrophilic gel by 30%. The xymedone release through the both hydrophilic and lipophilic membranes is described by a pseudo-second-order equation that typical for desorption process from the polymer matrix. The proposed partial validation protocol to assessing the drug release using the Franz cell can be useful for selection of optimal composition of dermal topical dosage forms with hydrophilic pharmaceutical active substances. Keywords: hydrogels, release, xymedone, zinc oxide nanoparticles, partial validation protocol
