title: Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery.
abstract: Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to first-pass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 23factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q24) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Heba M
authors.initials: HM
authors.lastname: Aboud
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: El Komy
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. adel.ali@pharm.bsu.edu.eg.
authors.forename: Adel A
authors.initials: AA
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Shahira F
authors.initials: SF
authors.lastname: El Menshawe
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abd Elbary
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D002227:Carbazoles; D008055:Lipids; D011412:Propanolamines; D013501:Surface-Active Agents; D000077261:Carvedilol; D020442:Poloxamer
keywords: bioavailability; carvedilol; factorial design; intranasal; solid lipid nanoparticles