Brain-targeting by optimized <sup>99m</sup>Tc-olanzapine: in vivo and in silico studies

Ibrahim, A. B.; Shamsel-Din, Hesham A.; Hussein, Ahmed; Salem, M. Alaraby

doi:10.1080/09553002.2020.1761568

Cited by 5 publications

(2 citation statements)

References 54 publications

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“…For maximizing the radiochemical yield, the influence of varying different reaction conditions (Na 2 S 2 O 4 concentration, ZT/ ZT-loaded terpesomes (ZT-T6) concentration, reaction medium pH, and reaction duration time) on the effectiveness of the radiolabeling technique was examined [ 27 ]. Experiments were carried out three times to examine the influence of each factor.…”

Section: Methodsmentioning

confidence: 99%

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Tawfik,

Eltaweel,

Fatouh

et al. 2023

Drug Deliv. and Transl. Res.

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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 23.31 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 (Q6h) were the selected dependent variables. Further morphological, crystallinity, and in-vivo histopathological studies were conducted for the optimum terpesomes (T6). 99mTc-ZT and 99mTc-ZT-T6 gel were radio-formulated for in-vivo biodistribution studies in mice following transdermal application of 99mTc-ZT-T6 gel, relative to 99mTc-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 Q6h (92.2%) with desirability value of 0.85. The safety of the developed T6 terpesomes was verified by the in-vivo histopathological studies. 99mTc-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 99mTc-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. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Tawfik,

Eltaweel,

Fatouh

et al. 2023

Drug Deliv. and Transl. Res.

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“…There are different methods of radiological technique to evaluate the in-vivo biodistribution as the drug radiolabeling, 40 radiolabeling of the optimized formula 14 or using radiolabeling indicator. 41 Merging between the radioisotopes (imaging https://doi.org/10.2147/IJN.S403707…”

Section: In-vivo Characterization Of the Optimized Clz-lbpm Formulamentioning

confidence: 99%

Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation

Elsharkawy¹,

Amin²,

Shamsel-Din³

et al. 2023

IJN

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The research objective is to design intranasal brain targeted CLZ loaded lecithin based polymeric micelles (CLZ-LbPM) aiming to improve central systemic CLZ bioavailability. Methods: In our study, intranasal CLZ loaded lecithin based polymeric micelles (CLZ-LbPM) were formulated using soya phosphatidyl choline (SPC) and sodium deoxycholate (SDC) with different CLZ:SPC:SDC ratios via thin film hydration technique aiming to enhance drug solubility, bioavailability and nose to brain targeting efficiency. Optimization of the prepared CLZ-LbPM using Design-Expert® software was achieved showing that M6 which composed of (CLZ:SPC: SDC) in respective ratios of 1:3:10 was selected as the optimized formula. The optimized formula was subjected to further evaluation tests as, Differential Scanning Calorimetry (DSC), TEM, in vitro release profile, ex vivo intranasal permeation and in vivo biodistribution. Results:The optimized formula with the highest desirability exhibiting (0.845), small particle size (12.23±4.76 nm), Zeta potential of (−38 mV), percent entrapment efficiency of > 90% and percent drug loading of 6.47%. Ex vivo permeation test showed flux value of 27 μg/cm².h and the enhancement ratio was about 3 when compared to the drug suspension, without any histological alteration. The radioiodinated clozapine ([ 131 I] iodo-CLZ) and radioiodinated optimized formula ([ 131 I] iodo-CLZ-LbPM) were formulated in an excellent radioiodination yield more than 95%. In vivo biodistribution studies of [ 131 I] iodo-CLZ-LbPM showed higher brain uptake (7.8%± 0.1%ID/g) for intranasal administration with rapid onset of action (at 0.25 h) than the intravenous formula. Its pharmacokinetic behavior showed relative bioavailability, direct transport percentage from nose to brain and drug targeting efficiency of 170.59%, 83.42% and 117% respectively. Conclusion:The intranasal self-assembling lecithin based mixed polymeric micelles could be an encouraging way for CLZ brain targeting.

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Gold nanoparticles for 99mTc-doxorubicin delivery: formulation, in vitro characterization, comparative studies in vivo stability and biodistribution

El-Safoury

Ibrahim

El-Setouhy

et al. 2021

J Radioanal Nucl Chem

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Brain-targeting by optimized ^99mTc-olanzapine: in vivo and in silico studies

Cited by 5 publications

References 54 publications

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation

Gold nanoparticles for 99mTc-doxorubicin delivery: formulation, in vitro characterization, comparative studies in vivo stability and biodistribution

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Brain-targeting by optimized 99mTc-olanzapine: in vivo and in silico studies

Cited by 5 publications

References 54 publications

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation

Gold nanoparticles for 99mTc-doxorubicin delivery: formulation, in vitro characterization, comparative studies in vivo stability and biodistribution

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Brain-targeting by optimized ^99mTc-olanzapine: in vivo and in silico studies