Preparation and biological evaluation of radioiodinated risperidone and lamotrigine as models for brain imaging agents

Saddar, Eman; El-Tawoosy, M.; Motaleb, H.A.

doi:10.1007/s10967-014-3139-5

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…RISP (Enke Pharma-Tech Co., Ltd., Cangzhou, China) was radiolabeled by direct electrophilic substitution with 125 I ( Figure 1 ) under oxidative conditions using a modified protocol derived from Saddar et al [ 30 ]. Given the very low solubility of RISP in aqueous solvents, we used Iodination Beads (ThermoFischer Sicentific, Waltham, MA, USA) to achieve mild oxidation conditions and permit a solid-supported reaction in a RISP powder suspension.…”

Section: Methodsmentioning

confidence: 99%

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

et al. 2023

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The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I− took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.

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Section: Methodsmentioning

confidence: 99%

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

et al. 2023

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“…The mean BA radioactivity uptake (%AD/g) in blood and liver was plotted against time (h). The total amount of blood radioactivity was calculated given that blood constitutes 7% of the mouse weight [64,65]. Pharmacokinetic characteristics of BA from blood and liver data were estimated for each mouse by using WinNonlin software program (version 1.5, Scientific Consulting Inc., Cary, NC, USA).…”

Section: Pharmacokinetic and Biodistribution Studiesmentioning

confidence: 99%

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

et al. 2020

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In this study, water-soluble chitosan lactate (CL) was reacted with lactobionic acid (LA), a disaccharide with remarkable affinity to hepatic asialoglycoprotein (ASGP) receptors, to form dual liver-targeting LA-modified-CL polymer for site-specific drug delivery to the liver. The synthesized polymer was used to encapsulate baicalin (BA), a promising bioactive flavonoid with pH-dependent solubility, into ultrahigh drug-loaded nanoparticles (NPs) via the ionic gelation method. The successful chemical conjugation of LA with CL was tested and the formulated drug-loaded LA-modified-CL-NPs were assessed in terms of particle size (PS), encapsulation efficiency (EE) and zeta potential (ZP) using full factorial design. The in vivo biodistribution and pharmacokinetics of the designed NPs were assessed using 99mTc-radiolabeled BA following oral administration to mice and results were compared to 99mTc-BA-loaded-LA-free-NPs and 99mTc-BA solution as controls. Results showed that the chemical modification of CL with LA was successfully achieved and the method of preparation of the optimized NPs was very efficient in encapsulating BA into nearly spherical particles with an extremely high EE exceeding 90%. The optimized BA-loaded-LA-modified-CL-NPs showed an average PS of 490 nm, EE of 93.7% and ZP of 48.1 mV. Oral administration of 99mTc-BA-loaded-LA-modified-CL-NPs showed a remarkable increase in BA delivery to the liver over 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA oral solution. The mean area under the curve (AUC0–24) estimates from liver data were determined to be 11-fold and 26-fold higher from 99mTc-BA-loaded-LA-modified-CL-NPs relative to 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA solution respectively. In conclusion, the outcome of this study highlights the great potential of using LA-modified-CL-NPs for the ultrahigh encapsulation of therapeutic molecules with pH-dependent/poor water-solubility and for targeting the liver.

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“…99m Tc-OLZ complex has higher brain uptake than other radio-labeled pharmaceuticals such as 99m Tc-ropinrole (4.87 ± 0.15% ID/g at 30 min) (Motaleb, Ibrahem, et al 2016) radioiodinated quinacrine based derivatives (6-Iodo-2methoxy-9-methylaminoacridine and 2,9-dimethoxy-6-iodo acridine) (3 ± 0.1% ID/g and 4.4 ± 0.12% % ID/g, 51 ± 0.18% ID/g at 10 min, respectively) (Saddar et al 2014) and 125 I-Zaleplon (4.4 ± 0.1% ID/g) (Amin et al 2013).…”

Section: Biological Distribution Study Of 99m Tc-olz Complexmentioning

confidence: 99%

“…The technology for brain diagnosis has become an important tool in both research and clinical care. Neuroscientists use that technology to visualize brain structure and function from the level of individual molecules to the whole brain, in order to recognize and diagnose neurological disorders, and develop new strategies for treatment (Saddar et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, several radiopharmaceuticals such as radioiodinated quinacrine derivatives (6-Iodo-2-methoxy-9-methylaminoacridine and 2,9-Dimethoxy-6-iodo acridine) (Fuchigami et al 2013), [ 125 I]-2-(2,20-bithiophen-5-yl)-6iodobenzo [d]thiazole (Cui et al 2010), benzofuran-2-yl(phenyl)methanone derivatives (Cui et al 2011), 125I-risperidone, 125I-lamotrigine (Saddar et al 2014) and 125 I-Zaleplon (Amin et al 2013) have been reported. They showed many disadvantages such as low brain-uptake (Amin et al 2013;Fuchigami et al 2013;Saddar et al 2014), low target-to-blood (T/B) ratio and very rapid blood clearance (few minutes) (Cui et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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

Ibrahim

Shamsel-Din

Hussein

et al. 2020

International Journal of Radiation Biology

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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.

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Preparation and biological evaluation of radioiodinated risperidone and lamotrigine as models for brain imaging agents

Cited by 7 publications

References 27 publications

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

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

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Preparation and biological evaluation of radioiodinated risperidone and lamotrigine as models for brain imaging agents

Cited by 7 publications

References 27 publications

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

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

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