title: PEGylated liposomes for topical vaginal therapy improve delivery of interferon alpha.
abstract: Recent studies regarding mucosal drug delivery indicate that nanosystems with surface-available polyethylene glycol (PEG) are able to penetrate mucus barrier, assure closer contact with the epithelium, and improve drug delivery to vagina. In the present work, we developed the mucus-penetrating PEGylated liposomes containing interferon alpha-2b (IFN α-2b), destined to provide localized therapy for human papilloma virus (HPV) vaginal infections. The PEGylated liposomes were of a mean size of 181±8nm, bearing a negative zeta potential of - 13mV and an entrapment efficiency of 81±10%. In vitro release experiments on model membrane showed a nearly non-existent IFN α-2b release from both the control and liposomally-associated IFN α-2b. However, the ex vivo penetration studies performed on the vaginal tissue obtained from pregnant sheep, showed the clear elevated IFN α-2b penetration from PEGylated liposomes as compared to the control. Furthermore, mucin studies confirmed the absence of interaction between the PEG-modified liposomes and mucin, confirming their ability to penetrate mucus and reach the deeper epithelium. The system holds a promise in improving topical delivery of IFN α-2b through enhanced efficacy of local anti-viral therapy.
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: may.w.joraholmen@uit.no.
authors.forename: May Wenche
authors.initials: MW
authors.lastname: Jøraholmen
authors.affiliation: Women's Health and Perinatology Research Group, Department of Clinical Medicine, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway; Department of Obstetrics and Gynecology, University Hospital of North Norway, Sykehusveien 5738, 9038 Tromsø, Norway. Electronic address: purusotam.basnet@uit.no.
authors.forename: Purusotam
authors.initials: P
authors.lastname: Basnet
authors.affiliation: Women's Health and Perinatology Research Group, Department of Clinical Medicine, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway; Department of Obstetrics and Gynecology, University Hospital of North Norway, Sykehusveien 5738, 9038 Tromsø, Norway; Department of Clinical Science, Intervention & Technology, Karolinska Institute, 141 86 Stockholm, Sweden. Electronic address: ganesh.acharya@uit.no.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Acharya
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: natasa.skalko-basnet@uit.no.
authors.forename: Nataša
authors.initials: N
authors.lastname: Škalko-Basnet
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008081:Liposomes; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012756:Sheep; D014621:Vagina
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008081:Liposomes; D011994:Recombinant Proteins; D011092:Polyethylene Glycols
keywords: Human papilloma virus; Interferon; Mucus-penetrating liposomes; PEGylated liposomes; Vaginal therapy