title: Zein-Based Nanoparticles Improve the Oral Bioavailability of Resveratrol and Its Anti-inflammatory Effects in a Mouse Model of Endotoxic Shock.
abstract: Resveratrol offers pleiotropic health benefits including a reported ability to inhibit lipopolysaccharide (LPS)-induced cytokine production. The aim of this work was to prepare, characterize, and evaluate a resveratrol nanoparticulate formulation based on zein. For this purpose, the oral bioavailability of the encapsulated polyphenol as well as its anti-inflammatory effects in a mouse model of endotoxic shock was studied. The resveratrol-loaded nanoparticles displayed a mean size of 307 ± 3 nm, with a negative zeta potential (-51.1 ± 1.55 mV), and a polyphenol loading of 80.2 ± 3.26 μg/mg. In vitro, the release of resveratrol from the nanoparticles was found to be pH independent and adjusted well to the Peppas-Sahlin kinetic model, suggesting a mechanism based on the combination of diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies demonstrated that zein-based nanoparticles provided high and prolonged plasma levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when administered in these nanoparticles increased up to 50% (19.2-fold higher than for the control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 days at 15 mg/kg were able to diminish the endotoxic symptoms induced in mice by the intraperitoneal administration of LPS (i.e., hypothermia, piloerection, and stillness). In addition, serum tumor necrosis factor-alpha (TNF-α) levels were slightly lower (approximately 15%) than those observed in the control.
authors.affiliation: †Department of Pharmacy and Pharmaceutical Technology, ‡Department of Microbiology, and #Centre for Nutrition Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Penalva
authors.affiliation: †Department of Pharmacy and Pharmaceutical Technology, ‡Department of Microbiology, and #Centre for Nutrition Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Esparza
authors.affiliation: †Department of Pharmacy and Pharmaceutical Technology, ‡Department of Microbiology, and #Centre for Nutrition Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Eneko
authors.initials: E
authors.lastname: Larraneta
authors.affiliation: †Department of Pharmacy and Pharmaceutical Technology, ‡Department of Microbiology, and #Centre for Nutrition Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: González-Navarro
authors.affiliation: †Department of Pharmacy and Pharmaceutical Technology, ‡Department of Microbiology, and #Centre for Nutrition Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamazo
authors.affiliation: †Department of Pharmacy and Pharmaceutical Technology, ‡Department of Microbiology, and #Centre for Nutrition Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Irache
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012772:Shock, Septic / Q000188:drug therapy*; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015028:Zein / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D015028:Zein; D000077185:Resveratrol
keywords: anti-inflammatory; bioavailability; nanoparticles; resveratrol; zein