Nanostructured lipid carriers-mediated brain delivery of carbamazepine for improved in vivo anticonvulsant and anxiolytic activity

Publication date: Available online 16 January 2020Source: International Journal of PharmaceuticsAuthor(s): Namrah Khan, Fawad Ali Shah, Isra Rana, Muhammad Mohsin Ansari, Fakhar ud Din, Syed Zaki Husain Rizvi, Waqar Aman, Gwan-Yeong Lee, Eun-Sun Lee, Jin-Ki Kim, Alam ZebAbstractThe limited brain delivery of carbamezapine (CBZ) presents a major hurdle in the successful epilepsy treatment. The potential of carbamezapine-loaded nanostructured lipid carriers (CBZ-NLCs) for improved brain delivery is investigated in the current study. CBZ-NLCs were prepared by using binary mixture of trilaurin and oleic acid as a lipid core stabilized with Poloxamer 188, Tween 80 and Span 80. CBZ-NLCs were evaluated for physicochemical properties, in vitro release, in vivo brain kinetics, anticonvulsant and anxiolytic activities. The optimized CBZ-NLCs demonstrated nanometric particle size (97.7 nm), surface charge of -22 mV and high drug incorporation (85%). CBZ-NLCs displayed biphasic release pattern with initial fast followed by sustained drug release. CBZ-NLCs significantly enhanced the AUC of CBZ (520.4 µg·h/mL) in brain compared with CBZ dispersion (244.9 µg·h/mL). In vivo anticonvulsant activity of CBZ-NLCs in PTZ-induced seizure model showed a significant increase in the onset time (143.0 sec) and reduction in duration (17.2 sec) of tonic-clonic seizures compared with CBZ dispersion (75.4 and 37.2 sec). The anxiolytic activity in light-dark box and elevated-plus maze models also demons...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research