title: Development of solid lipid nanoparticles as carriers for improving oral bioavailability of glibenclamide.
abstract: A solid lipid nanoparticle (SLN) formulation was developed with the aim of improving the oral bioavailability and the therapeutic effectiveness of glibenclamide (GLI), a poorly water-soluble drug used in the treatment of type 2 diabetes. The SLN was prepared using different lipid components (Precirol® and Compritol®) and preparation procedures. Precirol-based SLN, obtained with the emulsion of solvent evaporation technique gave the best results and was selected for drug loading. Addition of lecithin to the SLN core or PEG coating was effective in increasing the nanoparticles stability in simulated gastric solution. Both such formulations were stable after one month storage at 5±3°C, exhibited the absence of in vitro cytotoxicity, and presented a similar in vitro prolonged-release, reaching 100% release after 24h. The lecithin-containing GLI-loaded SLN formulation, selected for in vivo studies in virtue of its higher EE% than the PEG-coated formulation (70.3% vs 19.6%), showed a significantly stronger hypoglycemic effect with respect to the drug alone, in terms of both shorter onset time and longer duration of the effect. These positive results indicated that the proposed SLN approach was successful in improving GLI oral bioavailability, confirming its potential as an effective delivery system for a suitable therapy of diabetes.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: L M D
authors.initials: LM
authors.lastname: Gonçalves
authors.affiliation: Department of Chemistry, School of Sciences of Human Health, University of Florence, via Schiff 6, Sesto Fiorentino 50019, Florence, Italy. Electronic address: francesca.maestrelli@unifi.it.
authors.forename: F
authors.initials: F
authors.lastname: Maestrelli
authors.affiliation: Dept. of Neuroscience, Psychology, Drug Research and Child Health (Neurofarba)-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: Dept. of Neuroscience, Psychology, Drug Research and Child Health (Neurofarba)-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: A J
authors.initials: AJ
authors.lastname: Almeida
authors.affiliation: Department of Chemistry, School of Sciences of Human Health, University of Florence, via Schiff 6, Sesto Fiorentino 50019, Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mura
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D004075:Diglycerides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry; D005905:Glyburide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D004075:Diglycerides; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D007004:Hypoglycemic Agents; D008055:Lipids; C009032:precirol; D005905:Glyburide
keywords: Antiglycemic effect; Glibenclamide; PEG coating; Solid lipid nanoparticles; Stability