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Lung targeting was developed by synthesising pyrazolone derivatives 6a-f under solvent-free and thermal conditions by reacting azo coumarins 4a-c with hydrazines 5a and b using maltose as a biodegradable catalyst. Different spectral data characterized the synthesized agents as proton-NMR, FT-IR, and mass spectra. Direct radioiodination with iodine-131 was performed and optimized to reach the highest radiochemical purities (92 ± 0.47 to 98 ± 0.21%) using chloramine-T, a moderate oxidizing agent. The 131 I-pyrazolone derivatives were confirmed based on HRMS. Furthermore, radioiodinated nitro-derivatives accumulated well in the lung of normal mice during in vivo evaluation, and the better uptake was for nitrophenyl-derivative 7f, about 30.06 ± 0.04% at 30 min after injection. Consequently, synthesized radioiodinated derivatives may be employed as prospective tracers for lung perfusion scans., Competing Interests: Declaration of competing interest No conflicts of interest are declared by the authors and responsible for the material and writing., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Zolmitriptan (ZT) is a potent second generation triptan, commonly administered to alleviate migraine attacks. ZT suffers various limitations; massive hepatic first pass metabolism, P-gp efflux transporters susceptibility, and limited (≈40%) oral bioavailability. Transdermal route of administration could be explored to enhance its bioavailability. A 2 3 .3 1 full factorial design was constructed to developed twenty-four ZT loaded terpesomes via thin film hydration technique. The influence of drug: phosphatidylcholine ratio, terpene type, terpene concentration and sodium deoxycholate concentration on the characterization of the developed ZT-loaded terpesomes was assessed. Particle size (PS), zeta potential (ZP), ZT entrapment efficiency (EE%), drug loading (DL%) and drug released percentages after 6 h (Q 6h ) were the selected dependent variables. Further morphological, crystallinity, and in-vivo histopathological studies were conducted for the optimum terpesomes (T6). 99m Tc-ZT and 99m Tc-ZT-T6 gel were radio-formulated for in-vivo biodistribution studies in mice following transdermal application of 99m Tc-ZT-T6 gel, relative to 99m Tc-ZT oral solution. T6 terpesomes [comprising ZT and phosphatidylcholine (1:15), cineole (1% w/v) and sodium deoxycholate (0.1% w/v)] were optimum with respect to spherical PS (290.2 nm), ZP (-48.9 mV), EE% (83%), DL% (3.9%) and Q 6h (92.2%) with desirability value of 0.85. The safety of the developed T6 terpesomes was verified by the in-vivo histopathological studies. 99m Tc-ZT-T6 gel showed maximum brain concentration (5 ± 0.1%ID/ g) with highest brain to blood ratio of 1.92 ± 0.1 at 4 h post transdermal application. Significant improvement of ZT brain relative bioavailability (529%) and high brain targeting efficiency (315%) were revealed with 99m Tc-ZT-T6 gel, which confirmed successful ZT delivery to the brain. Terpesomes could be safe, successful systems capable of improving ZT bioavailability with high brain targeting efficiency., (© 2023. The Author(s).)

Migraine is a disabling neurovascular polygenic disorder affecting life quality with escorted socioeconomic encumbrances. Herein, we investigated the consolidated amalgamation of passive lipomer approach alongside active sonophoresis assisted transdermal delivery of zolmitriptan (ZT) using high frequency ultrasound pre-treatment protocol to mitigate migraine attacks. A modified nanoprecipitation technique was utilized to prepare zolmitriptan loaded lipomers (ZTL) adopting 2 3 factorial design. Three factors were scrutinized namely lipid type, ZT: lipid ratio and ZT: Gantrez® ratio. The prepared systems were characterized regarding particle size, zeta potential, polydispersity index, entrapment efficiency and in-vitro release studies. The best achieved ZTL system was evaluated for ZT- Gantrez® intermolecular interactions, drug crystallinity, morphology, ex-vivo permeation and histopathological examination. Finally, a comparative in-vivo biodistribution study through radiotracking technique using Technetium-99 m was adopted. L2 was the best-achieved ZTL system with respect to spherical particle size (390.7 nm), zeta-potential (-30.8 mV), PDI (0.2), entrapment efficiency (86.2%), controlled release profile, flux (147.13 μg/cm 2 /hr) and enhancement ratio (5.67). Histopathological studies proved the safety of L2 system upon application on skin. L2 revealed higher brain C max (12.21 %ID/g), prolonged brain MRT (8.67 hr), prolonged brain 0.23 hr), significantly high relative bioavailability (2929.36%) and similar brain T max (0.5 hr) compared to I.V. route with higher brain/blood ratio. Thus, sonophoresis assisted transdermal delivery of ZTL offers a propitious alterative to alleviate migraine symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The research objective is to design intranasal (IN) brain targeted CLZ-loaded polymeric nanomicellar systems (PNMS) aiming to improve central systemic CLZ bioavailability. Direct equilibrium method was used to prepare CLZ-PNMS using two hydrophobic poloxamines; Tetronic ® 904 (T904) and Tetronic ® 701 (T701) and one hydrophilic poloxamer; Synperonic ® PE/F127 (F127). Optimization is based on higher percent transmittance, solubilizing efficiency, and in vitro release after 24 h with smaller particle size was achieved using Design-Expert ® software. The optimized formula was further evaluated via TEM, ex vivo nasal permeation in addition to in vivo biodistribution using radiolabeling technique of the optimized formula by Technetium-99m ( 99m Tc). The optimized formula M5 has small size (217 nm) with relative high percentage of transmittance (97.72%) and high solubilization efficacy of 60.15-fold following 92.79% of CLZ released after 24 h. Ex vivo nasal permeation showed higher flux of 36.62 μg/cm 2 .h compared to 7.324 μg/cm 2 .h for CLZ suspension with no histological irritation. In vivo biodistribution results showed higher values of radioactivity percentage of the labeled optimized formula ( 99m Tc-M5) in brain and brain/blood ratio following IN administration of 99m Tc-M5 complex which were greater than their corresponding values following intravenous route. It is obvious that nasal delivery of CLZ-PNMS could be a promising way to improve central systemic CLZ bioavailability.

Tuberculosis (TB) is a disease caused by Mycobacterium and usually attack the lung. Synthesis of new dipeptide derivatives attached to antitubercular active heterocyclic rings like pyrazine and 1,3,4-oxadiazole called ethyl 2-(2-(5-((pyrazin-2-ylamino) methyl)-1,3,4-oxadiazol-2-ylthio) acetamido) acetamido)-3-(4-hydroxyphenyl) propanoate (EPOGTP) and iodinated EPOGTP are reported. The compounds have been characterized by mass, FT-IR and 1 H NMR spectroscopy. Their in vitro investigation against Mycobacterium tuberculosis cell line indicated good IC 50 value of 210 μg/ml for EPOGTP and 86 μg/ml for iodo-EPOGTP. For study the biodisriution, the direct radioiodination of EPOGTP with iodine-131 using mild oxidizing agent, N-Bromosuccinimide (NBS), was performed and optimized for obtaining the maximum radiochemical purity (97.3 ± 0.47%). Then, the in vivo biodistribution in healthy mice showed good accumulation of radioiodinated EPOGTP in lung of about 41.83 ± 0.23% (the percentage of injected dose per gram of organ) at 15 min post-injection. As a conclusion, the synthetized dipeptide and its iodinated derivative could be further evaluated as a potential antitubercular agents., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor is effective against Hepatitis B virus. Its poor oral bioavailability leads to frequent administration causing severe adverse effects. Thereby the entrapment of AD within lipid nanoparticulate systems is a way of increasing AD oral bioavailability as a result of improving intestinal permeability with efficient liver-targeted delivery together with higher drug stability during storage., Methods: AD-loaded nanostructured lipid carriers (AD-NLCs) were prepared via solvent emulsification diffusion technique adopting 2 4 full factorial design to study the effect of lipid percentage, presence of egg yolk lecithin, surfactant type and percentage on entrapment efficiency (E.E.%), particle size and percent in-vitro drug released after 8 h (Q8hrs)., Results: Formula (F12) showed E.E.% of 90.5 ± 0.2%, vesicle size of 240.2 ± 2.5 nm and Q8hrs of 58.55 ± 9.4% was selected as the optimum formula with desirability value of 0.757 based on highest EE%, lowest P.S. and Q8hrs. Further evaluation of the optimized formula using radioiodinated rose bengal (RIRB) in thioacetamide induced liver damage in Swiss Albino mice revealed a higher liver uptake of 22 ± 0.01% ID/g (percent injected dose/g organ) and liver uptake/Blood (T/B) ratio of 2.22 ± 0.067 post 2 h of I.V injection of RIRB compared to 9 ± 0.01% ID/g and 0.64 ± 0.017 in untreated group, respectively., Conclusion: NLCs could be successfully used as oral drug delivery carriers of the antiviral drug Adefovir Dipivoxil to the liver with higher stability and oral bioavailability. Graphical abstract.

A simple and efficient separation method of carrier-free 47 Sc from neutron irradiated titanium target using a novel chitosan-acrylic acid/multiwalled carbon nanotubes (CS-AA/MWCNTs) composite was established. The synthesis of the CS-AA/MWCNTs composite was achieved using gamma radiation-induced template polymerization. The grafting efficiency (GE%) of AA on CS onto the surface of f-MWCNTs reached a maximum of~84% under the optimized conditions (30 wt% CS, 1.0 wt% AA, 0.15 wt% f-MWCNTs, >0.2 wt% N,N'-Methylenebisacrylamide (NMBA), and irradiation dose ~25 kGy). Different analyses (FT-IR, SEM, TGA and DTA) were examined for confirming the structural morphology and mechanical properties of the new synthesized composite. Interestingly, the CS-AA/MWCNTs composite depicted a selective adsorption of Sc(III) rather than Ti(IV) ions at pH 5 with adsorption efficiency of ~93.93%. The ionic exchange separation of no-carrier-added (NCA) 47 Sc(III) from irradiated TiO 2 target on CS-AA/MWCNTs composite packed column efficiently eluted 47 Sc(III) by 91 ± 0.8% using 1 M HCl solution. The quality control tests (radionuclidic, radiochemical, and chemical purities) for the eluted 47 Sc(III) clarified its high purity and validity for cancer theranostics., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Olanzapine (OLZ) is an atypical antipsychotic agent that is characterized by low brain porousness. The present work aimed to develop radiolabeled olanzapine (OLZ) without colloidal impurities and evaluate its biodistribution following intravenous (I.V.) and intranasal (I.N.) administration as a potential agent for brain diagnosis. Materials and methods: OLZ was radiolabeled with technetium-99m by using sodium dithionite as the reducing agent. Biodistribution of 99m Tc-OLZ complex in mice following I.V. and I.N. administrations was examined. Furthermore, a molecular docking study was performed. Results: Sodium dithionite labeling procedure resulted in highest radiochemical yield (96.30 ± 0.09%) and in vitro stability in serum up to 8 h. Biodistribution study of 99m Tc-OLZ complex showed high brain uptake following I.N. (6.2 ± 0.12% ID/g) and I.V. (5.5 ± 0.09% ID/g) at 0.5 and 1 h post administration (P.I.), respectively. Docking into two brain targets predicts higher affinity of 99m Tc-OLZ than free OLZ. Additionally, docking to P-glycoproteins shows less affinity for the radiolabelled OLZ and hence it is expected to be associated with better brain exposure than free OLZ. Conclusion: These chemical and preliminary biological merits strongly suggest that the 99m Tc-OLZ complex with new reducing agent could be used as a potential diagnostic agent for brain.

The target of this study is the synthesis of a new diester derivative and radiolabeling with one of the most effective diagnostic radioisotopes to be investigated as a novel targeting radiotracer for tumor imaging. 10-[2-(9-Carboxynonanoyloxy)propoxy]-10-oxodecanoic acid was synthesized in excellent yield and characterized by Fourier-transform infrared spectroscopy, mass, 1 H-NMR, and 13 C-NMR spectra. The diester was technetium-99m ( 99m Tc) radiolabeled by direct technique using sodium dithionite as a reducing agent. The labeling parameters such as diester amount, reducing agent amount, pH of the medium, and reaction time were optimized. High radiochemical yield of 95.10 ± 0.41% and in vitro stability in serum up to 12 h have been obtained on complexation of the synthesized diester with Tc-99m. Evaluation of the diester anticancer activity against breast cancer cell line (MCF-7) showed high percent of inhibition about 61.5% at 100 μg/ml. The rhenium complex of the diester was synthesized and characterized by liquid chromatography-mass spectrometry (ESI) and elemental analysis depending on the strong chemical resemblance between Tc and Re. Biodistribution studies of 99m Tc-diester complex showed high target to nontarget ratio (T/NT) equals 6.24 ± 0.09 in tumor-bearing mice at 30-min postinjection, suggesting this complex could be used as hopeful solid tumor-imaging agent., (© 2020 John Wiley & Sons, Ltd.)

Azure-A is one of the phenothiazines (PTZs) derivatives which for decades have been used as antipsychotic drugs due to good lipophilic characteristics which enable them to pass through the blood brain barrier (BBB), besides the important property of enabeling investigation of the pathological forms of aggregated tau protein found in the neurons of the central nervous system. Radioiodination of Azure-A was carried out via an electrophilic substitution reaction using chloramine-T as oxidizing agent. The influence of various reaction parameters and conditions on radioiodination efficiency was investigated, and a high radiochemical yield of 92.07 ± 0.9 % was obtained. An in vitro cytotoxicity study of iodinated Azure-A on three cell lines (HCT-116, human colon carcinoma cell line; Hep-G2, liver carcinoma cell line and HFB-4, normal human melanocytes) was carried out, and the data revealed that ioiodinated Azure A has no to very low toxic effect. The in vivo biodistribution study of 131 I-Azure A showed a high brain uptake of 6.15 ± 0.09 % injected dose/g tissue organ at 30 minutes post-injection, and its retention in brain remained high up to 2 hours, whereas the clearance from the body appeared to proceed via the renal system. The experimental data were confirmed by the molecular docking studies to predict the effect of radioiodination on the binding affinity of the parent molecule (Azure A) to tau paired helical filaments (PHFs). Both ligands showed better binding to S2 and S3 pockets of (PHFs). Consequently, radioiodinated Azure A seems to be a good candidate as an imaging agent for taupathies such as Alzheimer's disease, chronic traumatic encephalopathy, and corticobasal degeneration. Furthermore, it could be a very potent theranostics agent for brain tumors., (© 2019 John Wiley & Sons, Ltd.)

Poly (acrylamide-acrylic Acid)/multi-walled carbon nanotubes composite [P(AAm-AA)/MWCNTs] was prepared by gamma radiation to initiate the copolymerization of AAm and AA onto MWCNTs surface. The structural characteristics were confirmed by FT-IR, SEM, XRD, TGA and DTA. The particle size distribution was determined by dynamic light scattering (DLS). [P(AAm-AA)/MWCNTs] was used to study the adsorption efficiency of 47 Sc from natural calcium by batch technique at different concentrations of HCl and/or HNO 3 acid solutions. No-carrier-added 47 Sc (III) was separated from 47 Ca(II) on [P(AAm-AA)/MWCNTs] column matrix. The elution efficiency of about 80 ± 1.5% was attained for 47 Sc(III) using 1M HNO 3 . Three quality control tests, radionuclidic, radiochemical and chemical purities were investigated to emphasis that 47 Sc secure for use in nuclear medicine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)