title: Novel carvedilol paediatric nanomicelle formulation: in-vitro characterization and in-vivo evaluation.
abstract: OBJECTIVE
  Carvedilol (CAR) is a poorly water-soluble beta-blocker. Its encapsulation within nanomicelles (NMs) could improve drug solubility and its oral bioavailability, allowing the development of a paediatric liquid CAR formulation with commercially available copolymers: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplus®).
  
  
  METHODS
  Drug-loaded NMs were prepared by copolymer and CAR dispersion in distilled water. Micellar size and morphology were characterized by dynamic light scattering and transmission electron microscopy, respectively. In-vitro drug permeation studies were evaluated by conventional gut sac method. In-vivo CAR oral bioavailability from NMs dispersions and drug control solution was evaluated in Wistar rats.
  
  
  RESULTS
  Carvedilol apparent aqueous solubility was increased (up to 60.4-folds) after its encapsulation within NMs. The micellar size was ranged between 10.9 and 81.9 nm with a monomodal size distribution. There was a significant enhancement of CAR relative oral bioavailability for both copolymers vs a micelle-free drug solution (P < 0.05). This improvement was higher for TPGS-based micelles (4.95-fold) in accordance with the in-vitro CAR permeation results.
  
  
  CONCLUSIONS
  The present investigation demonstrates the development of highly concentrated CAR liquid micellar formulation. The improvement on drug oral bioavailability contributes to the potential of this NMs formulation to enhance CAR paediatric treatment.
authors.affiliation: Faculty of Medical and Life Sciences, Hochschule Furtwangen University, Baden-Württemberg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Wegmann
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Luciano
authors.initials: L
authors.lastname: Parola
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Bertera
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|National Science Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Taira
authors.affiliation: National Science Research Council (CONICET), Buenos Aires, Argentina.|Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Cagel
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina.
authors.forename: Fabian
authors.initials: F
authors.lastname: Buontempo
authors.affiliation: National Science Research Council (CONICET), Buenos Aires, Argentina.|Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Bernabeu
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
authors.affiliation: National Science Research Council (CONICET), Buenos Aires, Argentina.|Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Chiappetta
authors.affiliation: National Science Research Council (CONICET), Buenos Aires, Argentina.|Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Moretton
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002227:Carbazoles / Q000737:chemistry* / Q000378:metabolism; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D008297:Male; D008823:Micelles; D046529:Microscopy, Electron, Transmission / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011412:Propanolamines / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014810:Vitamin E / Q000737:chemistry
chemical_list: D002227:Carbazoles; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011145:Polyvinyls; D011412:Propanolamines; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D000077261:Carvedilol; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan
keywords: carvedilol; nanomicelles; nanotechnology; oral bioavailability; paediatric pharmacotherapy