title: Nanotransfersomes of carvedilol for intranasal delivery: formulation, characterization and in vivo evaluation.
abstract: BACKGROUND
  Development of carvedilol-loaded transfersomes for intranasal administration to overcome poor nasal permeability and hepatic first pass effect so as to enhance its bioavailability.
  
  
  OBJECTIVE
  The purpose of this study was to develop carvedilol-loaded transfersomes containing different edge activators (EAs) then evaluating the in vivo behavior of the optimized formula in rabbits.
  
  
  METHODS
  The vesicles were prepared by incorporating different EAs including Span 20, Span 60, Tween 20, Tween 80, and sodium deoxycholate (SDC) in the lipid bilayer and each EA was used in three different ratios with respect to phosphatidylcholine (PC) including 95:5%, 85:15%, and 75:25% w/w (PC:EA). Evaluation of transfersomes was carried out in terms of shape, size, entrapment efficiency (EE), in vitro release, ex vivo permeation, confocal laser scanning microscopy (CLSM), and stability studies. The pharmacokinetic study of the optimized formula was conducted in rabbits.
  
  
  RESULTS
  The mean diameter of the vesicles was in the range of 295-443 nm. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% where Span 60 gave the highest values. Whereas those prepared using 85:15% w/w ratio showed highest percentages of drug release where SDC was superior to other EAs. The developed transfersomes exhibited significantly higher amounts of carvedilol permeated through nasal mucosa. CLSM of formula T14 containing SDC with 85:15% (w/w) (PC:EA) ratio revealed high permeation across the nasal mucosa.
  
  
  CONCLUSIONS
  The nanotransfersomal vesicles were significantly more efficient in nasal delivery of carvedilol with absolute bioavailability of 63.4%.
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Beni Suef University , Beni Suef , Egypt and.
authors.forename: Heba M
authors.initials: HM
authors.lastname: Aboud
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Beni Suef University , Beni Suef , Egypt and.
authors.forename: Adel Ahmed
authors.initials: AA
authors.lastname: Ali
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Beni Suef University , Beni Suef , Egypt and.
authors.forename: Shahira F
authors.initials: SF
authors.lastname: El-Menshawe
authors.affiliation: b Department of Pharmaceutics, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Ahmed Abd
authors.initials: AA
authors.lastname: Elbary
mesh_terms: D000818:Animals; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000077261:Carvedilol; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D065588:Nasal Absorption / Q000187:drug effects; D010316:Particle Size; D010539:Permeability; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D012869:Skin Absorption
chemical_list: D002227:Carbazoles; D004337:Drug Carriers; D011412:Propanolamines; D000077261:Carvedilol
keywords: Carvedilol; edge activators; intranasal; nanotransfersomes; pharmacokinetic study