title: Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jamia Hamdard (Hamdard University), Department of Pharmaceutics, Faculty of Pharmacy , M. B. Road, New Delhi 110062 , India +91 9811539489 ; yas2312003@yahoo.com.
authors.forename: Tausif
authors.initials: T
authors.lastname: Alam
authors.forename: Jayamanti
authors.initials: J
authors.lastname: Pandit
authors.forename: Divya
authors.initials: D
authors.lastname: Vohora
authors.forename: Mohd
authors.initials: M
authors.lastname: Aqil
authors.forename: Asgar
authors.initials: A
authors.lastname: Ali
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Sultana
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004827:Epilepsy / Q000188:drug therapy*; D066298:In Vitro Techniques; D000077213:Lamotrigine; D008055:Lipids / Q000737:chemistry; D008297:Male; D049329:Nanostructures; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008055:Lipids; D014227:Triazines; D000077213:Lamotrigine
keywords: brain delivery; epilepsy; intranasal delivery; lamotrigine; nanostructured lipid carriers