1. New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.
- Author
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Taleb A, Zhou YP, Meng LT, Zhu MY, Zhang Q, Naveed M, Li LD, Wang P, Zhou QG, Meng F, and Han F
- Subjects
- Animals, Anticonvulsants administration & dosage, Anticonvulsants adverse effects, Electroencephalography, Hindlimb Suspension, Hydrogels, Liposomes administration & dosage, Male, Maze Learning drug effects, Mice, Inbred C57BL, Open Field Test drug effects, Propoxycaine administration & dosage, Propoxycaine adverse effects, Mice, Anticonvulsants therapeutic use, Drug Delivery Systems methods, Epilepsy drug therapy, Propoxycaine therapeutic use
- Abstract
Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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