Preparation, characterization, and in vivo biodistribution study of intranasal 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 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 I using direct electrophilic substitution reaction. Quality control of I-CP was performed using different techniques. Different formulas of 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 I-CP, which inevitably decreased the nontarget effects of radioiodine. Intranasally administered 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 I-CP-loaded magnesomes can be a beneficial brain-targeting approach for improving the diagnosis and/or radiotherapy of certain brain diseases.