ESR INVESTIGATIONS of X-RAY EXPOSED DRUGS.

X-ray is used in several areas for analysis, imaging, sterilisation and security. X-ray machines are increasingly used in the entrance of the airports, shopping centres, etc. for security purposes. Therefore, human beings and belongings are frequently exposed to X-ray by transiting these checkpoints at various sites such as airports, shopping centres etc. This study aims is to investigate the X-rays potential effects (arising from security machines) on different groups of medicines which are analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), anti-diabetics (metformin HCl, pioglitazone), PPI's (lansoprazole, pantoprazole sesquihydrate), anti-hypertensives (losartan, clopidogrel hydrogen sulphate), heart failure medicines (verapamil HCl, spironolactone) used frequently and daily, by using ESR analysis. Coated acetylsalicylic acid tablets showed different intensities of ESR signals after 58 mGy irradiation. It thought to be the result of the coating polymer (Hydroxypropylmethylcellulose (HPMC)). According to the ESR results which were obtained for 0,24-58 mGy irradiated drugs- 1 hour after irradiation (refrigerated during this period) X-ray did not affect those medicines except the acetylsalicylic acid tablets significantly. The meaningful differences were only obtained between the non-irradiated, and 58 mGy irradiated acetylsalicylic acid tablets. Therefore, it can be concluded that X-ray exposed medicines, except coated acetylsalicylic acid tablets (after 58 mGy irradiation), can be used safely for the irradiation levels used in this study (0.24 mGy-0.58 mGy). In addition those data, ESR analyses were followed by other analysis such as FT-IR, DSC/TGA, dissolution, SEM, etc., and they are planned to be published soon.

A Comparative Study of Receptor-Targeted Magnetosome and HSA-Coated Iron Oxide Nanoparticles as MRI Contrast-Enhancing Agent in Animal Cancer Model.

Magnetosomes are specialized organelles arranged in intracellular chains in magnetotactic bacteria. The superparamagnetic property of these magnetite crystals provides potential applications as contrast-enhancing agents for magnetic resonance imaging. In this study, we compared two different nanoparticles that are bacterial magnetosome and HSA-coated iron oxide nanoparticles for targeting breast cancer. Both magnetosomes and HSA-coated iron oxide nanoparticles were chemically conjugated to fluorescent-labeled anti-EGFR antibodies. Antibody-conjugated nanoparticles were able to bind the MDA-MB-231 cell line, as assessed by flow cytometry. To compare the cytotoxic effect of nanoparticles, MTT assay was used, and according to the results, HSA-coated iron oxide nanoparticles were less cytotoxic to breast cancer cells than magnetosomes. Magnetosomes were bound with higher rate to breast cancer cells than HSA-coated iron oxide nanoparticles. While 250 µg/ml of magnetosomes was bound 92 ± 0.2%, 250 µg/ml of HSA-coated iron oxide nanoparticles was bound with a rate of 65 ± 5%. In vivo efficiencies of these nanoparticles on breast cancer generated in nude mice were assessed by MRI imaging. Anti-EGFR-modified nanoparticles provide higher resolution images than unmodified nanoparticles. Also, magnetosome with anti-EGFR produced darker image of the tumor tissue in T2-weighted MRI than HSA-coated iron oxide nanoparticles with anti-EGFR. In vivo MR imaging in a mouse breast cancer model shows effective intratumoral distribution of both nanoparticles in the tumor tissue. However, magnetosome demonstrated higher distribution than HSA-coated iron oxide nanoparticles according to fluorescence microscopy evaluation. According to the results of in vitro and in vivo study results, magnetosomes are promising for targeting and therapy applications of the breast cancer cells.

ESR investigations of gamma irradiated medical devices.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) biomaterials have been employed in recent years for periodontal procedures. In the present study, widely used dental GTR/GBR biomaterials (grafts: G1, G2, G3 and membranes: M1, M2, M3, M4) were exposed to gamma irradiation at an absorbed dose range of 0-50kGy and the radiolytic intermediates that have been created in the samples upon irradiation were characterized in detail by Electron Spin Resonance (ESR) spectroscopy. We aimed to standardize the measurement conditions for practical applications of gamma radiation sterilization of GTR/GBR biomaterials. We investigated the characteristic features of free radicals in gamma irradiated GTR/GBR biomaterials and examined the stability of the induced radicals at room temperature and accelerated stability conditions with ESR spectroscopy including dose-response curves, microwave power studies, dosimetric features of the biomaterials, variations of the peak heights with temperature, and long term stabilities of the radical species. Long-term stability studies have shown that G1 is quite stable even in accelerated storage conditions. The signal intensities of graft-type GTR/GBR biomaterials stored in normal and stability conditions have decreased very rapidly even only a few days after gamma irradiation sterilization. Thus, those samples indicating relatively low stability features can be very good candidates for the radiosterilization process. The beta-tricalcium phosphate and PLGA containing G1 and M1 respectively have found to be the most gamma stable bone substitute biomaterials and be safely sterilized by gamma radiation. ESR spectroscopy is an appropriate technique in giving important detailed spectroscopic findings in the gamma radiation sterilization studies of GTR/GBR biomaterials.

Gamma-irradiated liposome/noisome and lipogelosome/niogelosome formulations for the treatment of rheumatoid arthritis.

Treatment of rheumatoid arthritis by intraarticular administration of anti-inflammatory drugs encapsulated in drug delivery systems, such as liposomes/niosomes and lipogelosomes/niogelosomes, prolongs the residence time of the drugs in the joint. It was therefore anticipated that liposome/niosome entrapment would enhance the efficacy of drugs in the inflammatory sides. Liposomes are good candidates for the local delivery of therapeutic agents, such as diclofenac sodium (DFNa), for intraarticular delivery. Drugs for parenteral delivery must be sterile, and radiation sterilization is a method recognized by pharmacopoeias to achieve sterility of drugs. However, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the treatment, especially with the traditionally applied dose of 25 kGy. The present study aims to determine the effects of gamma irradiation on DFNa-loaded liposomes/niosomes and lipogelosomes/niogelosomes for the treatment of rheumatoid arthritis.

The effects of gamma irradiation on diclofenac sodium, liposome and niosome ingredients for rheumatoid arthritis.

The use of gamma rays for the sterilization of pharmaceutical raw materials and dosage forms is an alternative method for sterilization. However, one of the major problems of the radiosterilization is the production of new radiolytic products during the irradiation process. Therefore, the principal problem in radiosterilization is to determine and to characterize these physical and chemical changes originating from high-energy radiation. Parenteral drug delivery systems were prepared and in vitro characterization, biodistribution and treatment studies were done in our previous studies. Drug delivery systems (liposomes, niosomes, lipogelosomes and niogelosomes) encapsulating diclofenac sodium (DFNa) were prepared for the treatment of rheumatoid arthritis (RA). This work complies information about the studies developed in order to find out if gamma radiation could be applied as a sterilization method to DFNa, and the raw materials as dimyristoyl phosphatidylcholine (DMPC), surfactant I [polyglyceryl-3-cethyl ether (SUR I)], dicethyl phosphate (DCP) and cholesterol (CHOL) that are used to prepare those systems. The raw materials were irradiated with different radiation doses (5, 10, 25 and 50 kGy) and physicochemical changes (organoleptic properties pH, UV and melting point), microbiological evaluation [sterility assurance level (SAL), sterility and pyrogen test] and electron spin resonance (ESR) characteristics were studied at normal (25 °C, 60% relative humidity) and accelerated (40 °C, 75% relative humidity) stability test conditions.

Investigation of radiosterilization and dosimetric features of sulfacetamide sodium.

In the present work, the spectroscopic and kinetic features of the radical species induced in gamma-irradiated sulfacetamide-sodium (SS) was studied at room and at different temperatures in the dose range of 5-50kGy by electron spin resonance (ESR) technique with the aim of investigating the possibility of radiosterilization and dosimetric features of SS. A model consisting of four radical species of different spectroscopic features denoted as I-IV was found to describe best whole experimental data derived throughout the present work. These species were quite stable at room temperature but relatively unstable above room temperature. Heights of the characteristic resonance peaks measured with respect to the base line were considered to monitor microwave, temperature, time dependent and kinetic features of the radical species contributing to ESR spectrum. Collected experimental data were used to characterize the radical species responsible from ESR spectra through simulation calculations. Possible changes in the IR bands of gamma irradiated SS was also investigated by FT-IR technique, but no definite difference was observed between unirradiated and irradiated IR spectra of SS. As in other sulfonamides, radiation yield of solid SS was found to be very low (G

Spectroscopic features of radiolytic intermediates induced in gamma irradiated sulfatiazole: an ESR study.

Sulfonamides are used as active ingredients in different drugs to treat infections caused by bacteria. Sulfatiazole (STZ) is one of the commonly used sulfonamides as antibacterial agent in drugs, which constitute potential candidates for radiosterilization. However, the crucial point in this respect is to monitor the amount and characteristic features of the radiolytic intermediates produced after irradiation. Electron spin resonance (ESR) spectroscopy is extensively used for this purpose due to its high sensitivity toward intermediates exhibiting radicalic nature. Thus, the aim of the present work is to investigate the spectroscopic and kinetic features of the species having unpaired electrons induced in gamma irradiated STZ at room and different temperatures in the dose range of 5-50kGy using ESR spectroscopy. Spectra of irradiated STZ consisted of many resonance peaks in the studied dose and temperature ranges. Heights of the peaks measured with respect to the base line were used to monitor microwave, temperature, time-dependent features of the radical species contributing to the experimental ESR spectra. Four tentative species of different spectroscopic and structural features assigned as A, B, C and D were found well explaining the experimental ESR spectra of gamma irradiated STZ. Comparison between the principal IR bands of unirradiated and gamma irradiated samples showed no detectable changes and appearance of new bands.