Electron Beam Radiation as a Safe Method for the Sterilization of Aceclofenac and Diclofenac—The Usefulness of EPR and 1H-NMR Methods in Determination of Molecular Structure and Dynamics

Diclofenac (DC) [2-(2,6-Dichloroanilino)phenyl]acetic acid,) and aceclofenac (AC) 2-[2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxyacetic acid in substantia were subjected to ionizing radiation in the form of a beam of high-energy electrons from an accelerator in a standard sterilization dose of 25 kGy and higher radiation doses (50–400 kGy). We characterized non-irradiated and irradiated samples of DC and AC by using the following methods: organoleptic analysis (color, form), spectroscopic (IR, NMR, EPR), chromatographic (HPLC), and others (microscopic analysis, capillary melting point measurement, differential scanning calorimetry (DSC)). It was found that a absorbed dose of 50 kGy causes a change in the color of AC and DC from white to cream-like, which deepens with increasing radiation dose. No significant changes in the FT-IR spectra were observed, while no additional peaks were observed in the chromatograms, indicating emerging radio-degradation products (25 kGy). The melting point determined by the capillary method was 153.0 °C for AC and 291.0 °C for DC. After irradiation with the dose of 25 kGy for AC, it did not change, for DC it decreased by 0.5 °C, while for the dose of 400 kGy it was 151.0 °C and 286.0 °C for AC and DC, respectively. Both NSAIDs exhibit high radiation stability for typical sterilization doses of 25–50 kGy and are likely to be sterilized with radiation at a dose of 25 kGy. The influence of irradiation on changes in molecular dynamics and structure has been observed by 1H-NMR and EPR studies. This study aimed to determine the radiation stability of DC and AC by spectrophotometric, thermal and chromatographic methods. A standard dose of irradiation (25 kGy) was used to confirm the possibility of using this dose to obtain a sterile form of both NSAIDs. Higher doses of radiation (50–400 kGy) have been performed to explain the changes in DC and AC after sterilization

APTES-Modified SBA-15 as a Non-Toxic Carrier for Phenylbutazone

Improvement of the bioavailability of poorly soluble medicinal substances is currently one of the major challenges for pharmaceutical industry. Enhancing the dissolution rate of those drugs using novel methods allows to increase their bioavailability. In recent years, silica-based mesoporous materials have been proposed as drug delivery systems that augment the dissolution rate. The aim of this study was to analyse the influence of phenylbutazone adsorption on SBA-15 on its dissolution rate. Moreover, we examined the cytotoxicity of the analyzed silica. The material was characterized by SEM, TEM, DSC, 1H-NMR, XRD, and FT-IR. The phenylbutazone did not adsorb on unmodified SBA-15, while the adsorption on APTES-modified SBA-15 resulted in 50.43 mg/g of loaded phenylbutazone. Phenylbutazone adsorbed on the APTES-modified SBA-15 was then released in the hydrochloric acidic medium (pH 1.2) and phosphate buffer (pH 7.4) and compared to the dissolution rate of the crystalline phenylbutazone. The release profiles of the amorphous form of adsorbed phenylbutazone are constant in different pH, while the dissolution rate of the crystalline phenylbutazone depends on the pH. The cytotoxicity assays were performed using the Caco-2 cell line. Our results indicate that the analyzed material ensured phenylbutazone adsorption in an amorphous state inside the mesopores and increased its dissolution rate in various pH levels. Furthermore, the cytotoxicity assay proved safety of studied material. Our study demonstrated that APTES-modified SBA-15 can serve as a non-toxic drug carrier that improves the bioavailability of phenylbutazone

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma

Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAP:POPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC50 equal 2.9 ± 0.9 µM after 24 hours of incubation. Noteworthy, curcumin and orientin mixture in liposomal formulation exhibited a synergistic effect against GBM. Moreover, the impact on the expression of apoptosis-associated proteins (p53 and Caspase-3) of acteoside as well as curcumin and orientin mixture, as the most potent agents, was assessed, showing nearly 40% increase as compared to control U-138 MG and T98G cells. It should be emphasized that a new and alternative method of extrusion of the studied liposomes was developed