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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy.
Expert Opinion on Drug Delivery 2015 Februrary
OBJECTIVE: The aim of the present work was to investigate the efficacy of nanostructured lipid carriers (NLCs) to enhance the brain targeting of lamotrigine (LMT) following intranasal (IN) administration.
METHODS: Formulation was optimized using four-factor three levels Box- Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation. The developed formulation was subjected to stability study, in vivo efficacy and scintigraphic study in Wistar rat model.
RESULTS: The NLCs had a mean particle size of 151.6 ± 7.6 nm, polydispersity index of 0.249 ± 0.035, zeta potential of 11.75 ± 2.96 mV and EE of 96.64 ± 4.27%. The drug release from NLCs followed Fickian diffusion with a flux value of 11.73 μgcm(-2)h(-1). Sustained drug concentration was obtained in NLCs carrying LMT after IN administration after 24 h. γ scintigraphy studies further proved high accumulation of drug in brain.
CONCLUSION: Hence we can conclude that IN administration of LMT NLCs in rats is able to maintain higher brain concentration of LMT compared to IN and oral drug solution.
METHODS: Formulation was optimized using four-factor three levels Box- Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation. The developed formulation was subjected to stability study, in vivo efficacy and scintigraphic study in Wistar rat model.
RESULTS: The NLCs had a mean particle size of 151.6 ± 7.6 nm, polydispersity index of 0.249 ± 0.035, zeta potential of 11.75 ± 2.96 mV and EE of 96.64 ± 4.27%. The drug release from NLCs followed Fickian diffusion with a flux value of 11.73 μgcm(-2)h(-1). Sustained drug concentration was obtained in NLCs carrying LMT after IN administration after 24 h. γ scintigraphy studies further proved high accumulation of drug in brain.
CONCLUSION: Hence we can conclude that IN administration of LMT NLCs in rats is able to maintain higher brain concentration of LMT compared to IN and oral drug solution.
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