title: Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin.
abstract: The ability of a recently developed novel class of liposomes to promote dermal delivery of tretinoin (TRA) was evaluated. New penetration enhancer-containing vesicles (PEVs) were prepared adding to conventional phosphatidylcholine vesicles (control liposomes) different hydrophilic penetration enhancers: Oramix NS10 (OrNS10), Labrasol (Lab), Transcutol P (Trc), and propylene glycol (PG). Vesicles were characterized by morphology, size distribution, zeta potential, incorporation efficiency, stability, rheological behaviour, and deformability. Small, negatively charged, non-deformable, multilamellar vesicles were obtained. Rheological studies showed that PEVs had fluidity higher than conventional liposomes. The influence of the obtained PEVs on (trans)dermal delivery of tretinoin was studied by ex vivo diffusion experiments through new born pig skin using formulations having the drug both inside and outside the vesicles, having TRA only inside, in comparison with non-incorporated drug dispersions of the same composition used to produce the studied vesicles. Main result of these experiments was an improved cutaneous drug accumulation and a reduced transdermal TRA delivery (except for PG-PEVs). TRA deposition provided by PEVs was higher for dialysed than for non-dialysed vesicles. Further, the accumulation increased in the order: control liposomes<PG-PEVs<Trc-PEVs≤Or-PEVs<Lab-PEVs. SEM analysis of the skin gave evidence of PEVs' ability to strongly interact with the intercellular lipids causing an enlargement of this region.
authors.affiliation: Dept. Farmaco Chimico Tecnologico, Università degli Studi di Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
authors.forename: Chiara
authors.initials: C
authors.lastname: Sinico
authors.forename: Carla
authors.initials: C
authors.lastname: Caddeo
authors.forename: Amparo Ofelia
authors.initials: AO
authors.lastname: Vila
authors.forename: Donatella
authors.initials: D
authors.lastname: Valenti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D055598:Chemical Phenomena; D003956:Dialysis; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004339:Drug Compounding; D005026:Ethylene Glycols / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry; D005989:Glycerides; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D009930:Organic Chemicals / Q000737:chemistry; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D012212:Rheology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D034421:Sus scrofa; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D005026:Ethylene Glycols; D005960:Glucosides; D005989:Glycerides; D008081:Liposomes; D009930:Organic Chemicals; D014677:Pharmaceutical Vehicles; C509602:n-decyl-glucopyranoside; C440220:Labrasol; D014212:Tretinoin; C010111:carbitol