New frontier radioiodinated probe based on in silico resveratrol repositioning for microtubules dynamic targeting.

PURPOSE: As the 'de novo' drug discovery faces a highly attrition rates, drug repositioning procures a heighten concern in identifying novel uses for existing medications. This study aimed to fabricate radioiodinated resveratrol as a potent microtubules interfering agent for cancer theragnosis. METHODS: Resveratrol was radiolabeled with radioactive iodine where the radioiodination efficiency was enlightened and the computational approaches were employed to investigate the affinity and specificity with tubulins. Furthermore, the in-vivo distribution and pharmacokinetic studies in normal and tumor induced mice were investigated. RESULTS: The maximum radioiodination yield (94.6 ± 1.66) was achieved at optimum preparation parameters stated as 100 µg/mL of oxidizing agent, 100 µg/ml of resveratrol, reaction time of 30 min and reaction pH 5. The in silico studies showed that di-iodinated resveratrol (compound 6) exhibited the best binding score (-34.46) and interaction with the ß-tubulin binding site. The in vivo distribution in tumor models revealed a significant accumulation (4.02% ID/g) in tumor lesion at 60 min p.i. The rate of drug elimination demonstrated a mono-exponential decline of radioactivity versus time in the blood. CONCLUSION: Radioiodinated resveratrol revealed good microtubules targeting which render it as a novel theranostic probe for cancer management.

Evaluation of radioiodinated ethopabate as a potential tumor targeting agent.

Overexpression of folate synthesis and folate receptor in a wide variety of tumors was reported. As a result, folate derivatives have emerged as a potential candidate for tumor imaging and therapy. Ethopabate is a structural analogue of para-aminobenzoic acid (PABA), a precursor of folic acid. Ethopabate was radiolabeled with radioiodine-131 (131I) via direct electrophilic substitution reaction. Several factors that might affect the radiolabeling yield were studied. Paper chromatography was utilized for testing and evaluation of [131I]iodoethopabate, and HPLC was used as a co-chromatographic tool to confirm the radiochemical yield. The biodistribution of [131I]iodoethopabate in normal and tumor-bearing mice was investigated. The radioiodination of ethopabate resulted in a radiochemical yield of 93.70 ± 0.19%. The biodistribution data revealed that [131I]iodoethopabate was taken up by tumors with promising target/non-target (T/NT) ratios. Where, the tumor to-blood ratios were 3.30 ± 0.40 and 4.06 ± 0.10 at 1 and 4 h post injection, respectively. As a result of these findings, [131I]iodoethopabate appears to have excellent tumor uptake and adequate stability to be used for diagnostic purpose in the future.

Formulation of chitosan coated nanoliposomes for the oral delivery of colistin sulfate: in vitro characterization, 99mTc-radiolabeling and in vivo biodistribution studies.

Colistin sulfate is a very important antibiotic for the treatment of multidrug-resistant Gram-negative infections. Unfortunately, it has low oral bioavailability and several side effects following parenteral administration. The present study aims to develop chitosan-coated colistin nanoliposomes to improve the stability in the gastrointestinal tract and to enhance the oral delivery of colistin. The chitosan-coated colistin nanoliposomes were obtained via thin-film evaporation and electrostatic deposition methods using either Span 60, Tween 65 or Tween 80 as surfactants with different cholesterol: surfactant: soya lecithin ratios. The influence of systems variables was further characterized by vesicle size analysis, zeta potential (ZP), poly dispersibility index (PDI), and also their entrapment efficiency percentage (EE %) was evaluated. Various systems were formed with vesicle sizes in the nano-range, 155.64 ± 12.53 nm to 315.64 ± 15.90 nm, and EE % of 45.2 ± 2.9% to 81.8 ± 2.9%. Moreover, the ZP value of the prepared nanoliposomes switched from a negative to a positive value after chitosan coating. To track the released colistin in vivo, technetium 99m (99mTc) was incorporated into the optimum system (S-3) system via direct coupling with colistin. Chitosan-coated 99mTc-colistin nanoliposome, 99mTc-colistin suspension, and 99mTc-chitosan-coated nanoliposomes (placebo) were administered orally into bacterial infection (Escherichia coli) bearing mice. The biodistribution results showed that chitosan-coated nanoliposome significantly enhanced the bioavailability of colistin compared to colistin suspension (the commercially available). Moreover, the system effectively improved the localization of colistin at the infected muscle. In conclusion, this approach offers a promising tool for enhanced oral delivery of colistin.

Radioiodination and in vivo assessment of the potential of newly synthesized pyrrolizine-5-carboxamides derivative in tumor model.

Recently, pyrrolizine derivatives have been reported to possess numerous anticancer activities. In a previous study, (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine carboxamide (EZPCA) compound was synthesized and the cytotoxic activity of EZPCA toward COX-2 enzyme (overexpressed in cancer cells) was reported. In order to assess the suitability of this compound as a promising pilot structure for in vivo applications, EZPCA was radiolabeled with radioiodine-131 (131I) and various factors affecting radiolabeling process were studied. Quality control studies of [131I]iodo-EZPCA were performed using paper chromatography and HPLC was used as a co-chromatographic technique for confirming the radiochemical yield. Biodistribution studies of [131I]iodo-EZPCA were undertaken in normal and tumor bearing mice. The radiochemical yield percentage of [131I]iodo-EZPCA was 94.20 ± 0.12%. The biodistribution results showed evident tumor uptake of [131I]iodo-EZPCA with promising target/non-target (T/NT) ratios. As a conclusion, these data suggest that [131I]iodo-EZPCA had high binding efficiency, high tumor uptake and sufficient stability to be used be used in diagnostic studies.