Preparation and molecular modeling of radioiodopropranolol as a novel potential radiopharmaceutical for lung perfusion scan

Objective: Development of easy method for radioiodination of propranolol with high percent labeling yield for the purpose of lung perfusion imaging.Methods: Radioidination of propranolol was achieved using 125I via electrophilic substitution under the oxidative conditions of cholramine-T (CAT). All factors affecting the labeling procedure and labeling yield were studied. Paper electrophoresis and HPLC were performed to determine the radiochemical yield and purity of the 125I-propranolol. Molecular modeling and docking studies were performed to ensure the binding of the newly obtained 125I-propranolol to beta-2 (β2) adrenergic receptor.Results: Radioiodination of propranolol has been successfully achieved with high labeling yield (93.7 ± 0.81% ) . 125I-propranolol was stable for 24 h when kept in dark at ambient temperature. Biodistribution studies showed lung uptake of 21.60 ± 0.03% injected dose/g  (%ID/g) at 30 min post-injection. Molecular modeling confirmed that radioiodination did not affect the binding of propranolol to β2- receptor.Conclusion: Iodopropranolol can be considered as good potential lung perfusion agent as suggested by the results of biodistribution and molecular modeling studies

Tailoring of Selenium-Plated Novasomes for Fine-Tuning Pharmacokinetic and Tumor Uptake of Quercetin: In Vitro Optimization and In Vivo Radiobiodistribution Assessment in Ehrlich Tumor-Bearing Mice

Quercetin (QRC) is a bioflavonoid with anti-inflammatory, antioxidant, and anticancer activities, yet QRC poor bioavailability has hampered its clinical implementation. The aim of the current work was to harness novasomes (NOVs), free fatty acid enriched vesicles, as a novel nano-cargo for felicitous QRC delivery with subsequent functionalization with selenium (SeNOVs), to extend the systemic bio-fate of NOVs and potentiate QRC anticancer efficacy through the synergy with selenium. QRC-NOVs were primed embedding oleic acid, Brij 35, and cholesterol adopting thin-film hydration technique according to Box–Behnken design. Employing Design-Expert® software, the impact of formulation variables on NOVs physicochemical characteristics besides the optimum formulation election were explored. Based on the optimal NOVs formulation, QRC-SeNOVs were assembled via electrostatic complexation/in situ reduction method. The MTT cytotoxicity assay of the uncoated, and coated nanovectors versus crude QRC was investigated in human rhabdomyosarcoma (RD) cells. The in vivo pharmacokinetic and biodistribution studies after intravenous administrations of technetium-99m (99mTc)-labeled QRC-NOVs, QRC-SeNOVs, and QRC-solution were scrutinized in Ehrlich tumor-bearing mice. QRC-NOVs and QRC-SeNOVs disclosed entrapment efficiency of 67.21 and 70.85%, vesicle size of 107.29 and 129.16 nm, ζ potential of −34.71 and −43.25 mV, and accumulatively released 43.26 and 31.30% QRC within 24 h, respectively. Additionally, QRC-SeNOVs manifested a far lower IC50 of 5.56 μg/mL on RD cells than that of QRC-NOVs (17.63 μg/mL) and crude QRC (38.71 μg/mL). Moreover, the biodistribution study elicited higher preferential uptake of 99mTc-QRC-SeNOVs within the tumorous tissues by 1.73- and 5.67-fold as compared to 99mTc-QRC-NOVs and 99mTc-QRC-solution, respectively. Furthermore, the relative uptake efficiency of 99mTc-QRC-SeNOVs was 5.78, the concentration efficiency was 4.74 and the drug-targeting efficiency was 3.21. Hence, the engineered QRC-SeNOVs could confer an auspicious hybrid nanoparadigm for QRC delivery with fine-tuned pharmacokinetics, and synergized antitumor traits