title: Nose to Brain Delivery of Midazolam Loaded PLGA Nanoparticles: In Vitro and In Vivo Investigations.
abstract: OBJECTIVE
  The present study is aimed to develop poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NP) loaded with midazolam (Mdz) for nose to brain delivery.
  
  
  METHODS
  NP were formulated by nanoprecipitation and characterized for z-average, zeta potential, % drug entrapment and ex vivo drug release. Mdz NP (MNP) were radiolabeled with technetium-99m. Biodistribution and gamma scintigraphic studies were performed on Sprague-Dawley rats following intranasal (i.n) and intravenous (i.v) administration to trace the transport of Mdz for nose-to-brain delivery.
  
  
  CONCLUSIONS
  MNP showed z-average of 164±4.5nm with polydispersity index 0.099±0.02 and zeta potential of -16.6±2.5mV. Ex vivo drug studies indicated that MNP showed 29±1.2% of permeation upto 4h via sheep nasal mucosa, whereas Mdz suspension (MS) showed drug release of 83±1.2% within 4h. Comparing i.n administration of MNP, MS and i.v administration of MS, scintigraphy imaging and Brain/blood uptake ratios indicated higher brain targeting via i.n administration of MNP.
  
  
  CONCLUSIONS
  Results indicated that the i.n MNP could be employed as a non invasive mode of delivery system with improved drug entrapment, stability and controlled drug release over a period of time.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Dhruv K
authors.initials: DK
authors.lastname: Nishad
authors.forename: Thakuri
authors.initials: T
authors.lastname: Singh
authors.forename: Reema
authors.initials: R
authors.lastname: Gabrani
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector 62, Noida, UP-201307, India. shweta.dang@jiit.ac.in.
authors.forename: Shweta
authors.initials: S
authors.lastname: Dang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D019344:Lactic Acid; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053758:Nanoparticles; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D006993:Hypnotics and Sedatives; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008874:Midazolam