title: Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.
abstract: Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (<200nm) as determined by dynamic light scattering technique and transmission electron microscopy, assured transcellular transport across olfactory axons whose diameter was ≈200nm and then paving a direct path to brain. TFB-NPs and TFB-SLNs resulted in 64.11±2.21% and 57.81±5.32% entrapment efficiencies respectively which again asserted protection of drug from chemical and biological degradation in nasal cavity. In vitro release studies proved the sustained release of TFB from TFB-NPs and TFB-SLNs in comparison with pure drug, indicating prolonged residence times of drug at targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Eameema
authors.initials: E
authors.lastname: Muntimadugu
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Raju
authors.initials: R
authors.lastname: Dhommati
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Venu Gopala Swami
authors.initials: VG
authors.lastname: Challa
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: M
authors.initials: M
authors.lastname: Shaheen
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: wahid@niperhyd.ac.in.
authors.forename: Wahid
authors.initials: W
authors.lastname: Khan
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D008055:Lipids; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C505522:tarenflurbil; D005480:Flurbiprofen
keywords: Alzheimer's disease; Brain targeting; Nanoparticles; Nose to brain delivery; Pharmacokinetics; Tarenflurbil