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Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc‐radiolabeled and tofacitinib citrate‐encapsulated microsphere loaded poloxamer in situ gel formulations for the intra‐articular treatment. Among nine different microsphere formulations, MS/TOFA‐9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra‐articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA‐9 and PLX‐MS/TOFA‐9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti‐inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc‐MS/TOFA‐9 and 99mTc‐PLX‐MS/TOFA‐9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX‐MS/TOFA‐9 was found to be a promising agent for intra‐articular injection in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Cancer is still a global health problem. Among cancer types, breast cancer is the most frequently diagnosed one, and it causes a high mortality rate if not diagnosed in the early stages. In our study, imatinib encapsulated, nanosized, neutral/cationic liposome formulations were prepared as theranostic agents for breast cancer. After the characterization studies in which all liposomes exhibited proper profile owing to their particle size between 133 and 250 nm, polydispersity index values lower than 0.4, neutral and cationic zeta potential values, and high drug encapsulation efficiency, controlled drug release behaviors with zero‐order kinetic were obtained. The higher than 90% radiolabeling efficiency values were obtained thanks to the determination of optimum radiolabeling condition (80°C temperature, 5 mCi radioactivity, and 10 min incubation period). According to the resazurin assay evaluating the cytotoxic profile of liposomes on MCF7 cells, neutral empty liposome was found as biocompatible, while both cationic liposomes (empty and drug‐loaded ones) exhibited high nonspecific cytotoxicity at even low drug concentration due to the existence of stearyl amine in the formulations. However, dose‐dependent cytotoxic effect and the highest cellular binding capacity were obtained by imatinib loaded neutral liposomes. In conclusion, 68Ga‐radiolabeled, imatinib‐loaded, neutral, nanosized liposome formulation is the most promising one as a theranostic agent among all formulations. [ABSTRACT FROM AUTHOR]

Infectious diseases are still the major issue not only due to antibiotic resistance but also causing deaths if not diagnosed at early-stages. Different approaches including nanosized drug delivery systems and theranostics are researched to overcome antibiotic resistance, decrease the side effects of antibiotics, improve the treatment response, and early diagnose. Therefore, in the present study, nanosized, radiolabeled with 99mTc, colistin encapsulated, neutral and cationic liposome formulations were prepared as the theranostic agent for Pseudomonas aeruginosa infections. Liposomes exhibited appropriate physicochemical properties thanks to their nano-particle size (between 173 and 217 nm), neutral zeta potential value (about − 6.5 and 2.8 mV), as well as encapsulation efficiency of about 75%. All liposome formulations were radiolabeled with over 90% efficiency, and the concentration of stannous chloride was found as 1 mg.mL−1 to obtain maximum radiolabeling efficiency. In alamar blue analysis, neutral liposome formulations were found more biocompatible compared with the cationic formulations. Neutral colistin encapsulated liposomes were found to be more effective against P. aeruginosa strain according to their time-dependent antibacterial effect, in addition to their highest bacterial binding capacity. As conclusion, theranostic, nanosized, colistin encapsulated, neutral liposome formulations were found as promising agents for the imaging and treating of P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

Aim: Exendin-4 is a type 2 diabetes antidiabetic drug that is a peptide agonist of the glucagon-like peptide 1 receptor (GLP-1R). Up to date, different exendin-4 compounds have been radiolabeled with many radioisotopes such as 68Ga, 18F, 64Cu and 99mTc for various purposes like study of over expression of GLP-1R in insulinoma. The purpose of this study is to radiolabel exendin-4 with 99mTc under appropriate conditions. Methods: In this study, exendin-4 was labeled with 99mTc, and quality control tests of 99mTc-exendin-4 were done using ascending radioactive thin layer chromatography (RTLC). Also, the effects of important parameters such as the amount of reducing agent, pH value, incubation time, and radiation dose on the labeling efficiency were investigated. Then, the stability of 99mTc-exendin-4 was assessed. Results: According to the results, 99mTc-exendin-4 was prepared with over 95 percent labeling efficiency by a novel, easy, and quick direct method with 30-min incubation time at pH 6.6. To achieve the best radiolabeling condition; 10 µg of exendin-4, 50 µg of stannous chloride (reducing agent) and 37 MBq 99mTc was used. The RTLC studies indicated that 99mTc-exendin-4 is stable up to 6 h in room temperature. Conclusion: The obtained results demonstrated that radiolabeled exendin-4 may be a promising agent for GLP-1R imaging studies. Further studies are in progress in order to evaluate receptor binding capacity and biodistribution of the complex in experimental animals. [ABSTRACT FROM AUTHOR]

In the present study Tc-MTX was prepared with high labeling yield by a new simple and easy formulation method. According to cell culture studies, Tc-MTX incorporated with both MCF-7 and CRL8798 cells, with significant differences in the uptake percentages. Since Tc-MTX highly uptake in cancer cell line, the results demonstrated that radiolabeled MTX may be promising for breast cancer diagnosis of oncological patients. [ABSTRACT FROM AUTHOR]

The purpose of this work is to prepare a self-microemulsifying drug delivery system (SMEDDS) for risedronate sodium (RSD) and to compare the permeability with RSD solution. The solubility of RSD was determined in different vehicles. Phase diagrams were constructed to determine the optimum concentration of oil, surfactant, and cosurfactant. RSD SMEDDS was prepared by using a mixture of soybean oil, cremophor EL, span 80, and transcutol (2.02:7.72:23.27:61.74, w/w, respectively). The prepared RSD SMEDDS was characterized by droplet size value.In vitroCaco-2 cell permeability studies were performed for SMEDDS and solution of radioactive (99 mTc-labeled RSD) and nonradioactive RSD. The experimental results indicated that RSD SMEDDS has good stability and its droplet size is between 216.68 ± 3.79 and 225.26 ± 7.65 during stability time. In addition, RSD SMEDDS has higher permeability value than the RSD solution for both radioactive and nonradioactive experiments. The results illustrated the potential use of SMEDDS for delivery of poorly absorbed RSD. [ABSTRACT FROM AUTHOR]