title: Freeze-dried eudragit-hyaluronan multicompartment liposomes to improve the intestinal bioavailability of curcumin.
abstract: This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to increase their stability, led to a reduction of vesicle size and a good homogeneity of the systems, after simple rehydration with water. X-ray diffraction study demonstrated that after the freeze-drying process, curcumin remained successfully incorporated within the vesicles. All the vesicles displayed similar features: size ranging from 220 to 287nm, spherical or oval shape, multilamellar or large unilamellar morphology with a peculiar multicompartment organization involving 1-4 smaller vesicles inside. In vitro studies demonstrated the ability of the combined polymers to protect the vesicles from the harsh conditions of the gastro-intestinal tract (i.e., ionic strength and pH variation), which was confirmed in vivo by the greater deposition of curcumin in the intestinal region, as compared to the free drug in dispersion. This enhanced accumulation of curcumin provided by the eudragit-hyaluronan immobilized vesicles, together with an increase in Caco-2 cell viability exposed to hydrogen peroxide, indicated that vesicles can ensure a local protection against oxidative stress and an increase in its intestinal absorption.
authors.affiliation: Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Ana
authors.initials: A
authors.lastname: Catalan-Latorre
authors.affiliation: Dept. of Food Science and Technology, University of Kurdistan, 66177-15177 Pasdaran Street, Sanandaj, Kurdistan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ravaghi
authors.affiliation: Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy. Electronic address: mlmanca@unica.it.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.affiliation: Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Caddeo
authors.affiliation: Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Marongiu
authors.affiliation: Biopharmaceutics and Pharmacokinetics Unit, Institute for Nanoscience and Nanotechnology, University of Barcelona, Barcelona, Spain.
authors.forename: Guido
authors.initials: G
authors.lastname: Ennas
authors.affiliation: Biopharmaceutics and Pharmacokinetics Unit, Institute for Nanoscience and Nanotechnology, University of Barcelona, Barcelona, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Escribano-Ferrer
authors.affiliation: Dept. of Pharmacy and Pharmaceutical Technology, University of Valencia, Avda Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: José Esteban
authors.initials: JE
authors.lastname: Peris
authors.affiliation: Dept. of Pharmacy and Pharmaceutical Technology, University of Valencia, Avda Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain; Instituto de Reconocimiento Molecular y Desarrollo Tecnológico, Centro Mixto Universidad Politécnica de Valencia-Universidad de Valencia, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Diez-Sales
authors.affiliation: Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.affiliation: Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
mesh_terms: D000818:Animals; D001682:Biological Availability; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005612:Freeze Drying; D006820:Hyaluronic Acid / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D011109:Polymethacrylic Acids / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D006820:Hyaluronic Acid; D003474:Curcumin
keywords: Antioxidant; Curcumin; Intestinal biodistribution; Liposome; Polymer