title: New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis.
abstract: We evaluated the benefits of a novel formulation of vasoactive intestinal peptide (VIP) based on the incorporation of VIP-loaded rhodamine-conjugated liposomes (VIP-Rh-Lip) within hyaluronic acid (HA) gel (Gel-VIP-Rh-Lip) for the treatment of endotoxin-induced uveitis (EIU) in comparison with VIP-Rh-Lip alone. In vitro release study and rheological analysis showed that interactions between HA chains and liposomes resulted in increased viscosity and reinforced elasticity of the gel. In vivo a single intravitreal injection of Gel-VIP-Rh-Lip was performed in rats 7 days prior to uveitis induction by subcutaneous lipopolysaccharide injection. The maximal ocular inflammation occurs within 16-24 h in controls (VIP-Rh-Lip, unloaded-Rh-Lip). Whereas intraocular injection of VIP-Rh-Lip had no effect on EIU severity compared with controls, Gel-VIP-Rh-Lip reduced significantly the clinical score and number of inflammatory cells infiltrating the eye. The fate of liposomes, VIP and HA in the eyes, regional and inguinal lymph nodes and spleen was analyzed by immunostaining and fluorescence microscopy. Retention of liposomes by HA gel was observed in vitro and in vivo. Inflammation severity seemed to impact on system stability resulting in the delayed release of VIP. Thus, HA gel containing VIP-Rh-Lip is an efficient strategy to obtain a sustained delivery of VIP in ocular and lymph node tissues.
authors.affiliation: Univ Paris Sud 11, Physico-chimie-Pharmacotechnie-Biopharmacie, Faculté de Pharmacie, F-92296 Châtenay-Malabry, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Lajavardi
authors.forename: Serge
authors.initials: S
authors.lastname: Camelo
authors.forename: Florence
authors.initials: F
authors.lastname: Agnely
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Brigitte
authors.initials: B
authors.lastname: Goldenberg
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Naud
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Kozak
authors.forename: Amélie
authors.initials: A
authors.lastname: Bochot
mesh_terms: D000465:Algorithms; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004548:Elasticity; D004731:Endotoxins; D005452:Fluoresceins / Q000737:chemistry; D005782:Gels; D006820:Hyaluronic Acid / Q000737:chemistry*; D007267:Injections; D008081:Liposomes; D008297:Male; D010316:Particle Size; D051381:Rats; D011917:Rats, Inbred Lew; D012212:Rheology; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage* / Q000627:therapeutic use; D014783:Viscosity; D014822:Vitreous Body
chemical_list: D004337:Drug Carriers; D004731:Endotoxins; D005452:Fluoresceins; D005782:Gels; D008081:Liposomes; D014660:Vasoactive Intestinal Peptide; D006820:Hyaluronic Acid; C007740:fluorexon