title: Penetration Enhancer-Containing Vesicles: Does the Penetration Enhancer Structure Affect Topical Drug Delivery?
abstract: The aim of this study was to elucidate the influence of the edge activator structure on the properties of novel deformable liposomes, Penetration Enhancer-containing Vesicles (PEVs), capable of delivering drugs to the skin. The PEVs were prepared by testing five different amphiphilic penetration enhancers as edge activators in the bilayer composition, together with soy phosphatidylcholine and oleic acid. The penetration enhancers contained the same lipophilic tail (one or more C8-C10 carbon chains) and different hydrophilic heads. Conventional phospholipid liposomes were prepared and used as a control. Lidocaine was chosen as a model drug. Liquid and gelified PEVs were obtained, depending on the penetration enhancer used. The vesicular systems were characterized by measuring size distribution, zeta potential, incorporation efficiency, and monitoring these parameters over 90 days. Accelerated ageing tests were also performed to check the stability of the dispersions. The effects of the different nature of the edge activator on the features of the obtained PEVs were assessed by TEM, SAXS and WAXS, rheological and deformability studies. Higher interactions of the most lipophilic penetration enhancers with the lipid bilayers and a consequent higher stability and elasticity of the obtained PEVs were observed. In vitro experiments through pig skin confirmed the superior potential as carriers for lidocaine of the PEVs prepared with the most lipophilic penetration enhancers, even in comparison with commercial EMLA cream.
authors.forename: Carla
authors.initials: C
authors.lastname: Caddeo
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
authors.forename: Chiara
authors.initials: C
authors.lastname: Sinico
authors.forename: Donatella
authors.initials: D
authors.lastname: Valenti
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.forename: Maura
authors.initials: M
authors.lastname: Monduzzi
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, University of Cagliari, CNBS, Via Ospedale 72, 09124 Cagliari, Italy. mfadda@unica.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D010316:Particle Size; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
chemical_list: D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D010743:Phospholipids; D008012:Lidocaine