Open AccessIn‐vitro and in‐vivo evaluation of chitosan‐based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus
Author(s) -
Taymouri Somayeh,
Minaiyan Mohsen,
Ebrahimi Farnaz,
Tavakoli Naser
Publication year - 2020
Publication title -
iet nanobiotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.366
H-Index - 38
eISSN - 1751-875X
pISSN - 1751-8741
DOI - 10.1049/iet-nbt.2019.0156
Subject(s) - chitosan , in vivo , zeta potential , pharmacology , nasal administration , chemistry , materials science , anticonvulsant , chromatography , medicine , organic chemistry , nanoparticle , nanotechnology , epilepsy , microbiology and biotechnology , psychiatry , biology
The objective of this study was to develop an in‐situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose‐to‐brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in‐situ gels containing LZM‐NLCs were prepared using a combination of chitosan and β‐glycerol phosphate (β‐GP). The anticonvulsant efficacy of LZM‐NLCs‐Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of −20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) β‐GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in‐vivo findings showed that compared with the control group and the group that received LZM‐Gel, the occurrence of PTZ‐induced seizures in the rats was significantly reduced by LZM‐NLCs‐Gel after intranasal administration. These results, therefore, suggested that the LZM‐NLCs‐Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.