Preparation, characterization, and in vivo biodistribution study of intranasal 131 I-clonazepam-loaded phospholipid magnesome as a promising brain delivery system.

Objective: Clonazepam (CP) is a potent long-acting nitrobenzodiazepine derivative that could be used for targeting peripheral benzodiazepine receptors. Phospholipid magnesome is a new vesicular nanosystem recently developed for brain targeting. Improving the uptake of ¹³¹ I-CP to the brain might be effective for the diagnosis and/or radiotherapy of certain brain diseases and/or tumors.
Methods: CP was radiolabeled with ¹³¹ I using direct electrophilic substitution reaction. Quality control of ¹³¹ I-CP was performed using different techniques. Different formulas of ¹³¹ I-CP were prepared and characterized according to particle size and polydispersity index. The structural features of the optimized formula were then interpreted using transmission electron microscopy and scanning electron microscopy, whereas pharmacokinetic and in vivo behaviors were estimated using the intravenous and intranasal delivery routes.
Results: The heart and blood demonstrated lower uptake of ¹³¹ I-CP, which inevitably decreased the nontarget effects of radioiodine. Intranasally administered ¹³¹ I-CP-loaded magnesomes (INMg) had noticeably higher brain uptake (7.1 ± 0.09%ID/g) with rapid onset of action within 5 min and effective pharmacokinetic behavior. INMg had a drug targeting efficiency and nose-to-brain direct transport percentage of 121.1% and 94.6%, respectively as well as a relative bioavailability of 441.04 ± 75.5%.
Conclusion: The present study showed that ¹³¹ I-CP-loaded magnesomes can be a beneficial brain-targeting approach for improving the diagnosis and/or radiotherapy of certain brain diseases.
(Copyright © 2021. Published by Elsevier B.V.)