title: Development of intranasal nanovehicles of itraconazole and their immunological activities for the therapy of rhinovirus infection.
abstract: Itraconazole (ITZ)-loaded microemulsion (ME) systems for intranasal (IN) delivery were developed for the treatment of human rhinovirus serotype 1B (HRV1B) infection. ITZ was incorporated into the oil-in-water (o/w) ME formulation composed of benzyl alcohol (oil), Cremophor EL (surfactant), Solutol HS15 (cosurfactant), and water. The optimized composition of ME was determined by constructing pseudo-ternary phase diagram. ITZ ME formulation with about 150nm mean diameter and spherical shape was prepared and the solubility of ITZ in blank ME was markedly improved (up to 13.9mg/mL). The initial value of droplet size was maintained with four times dilution in the aqueous buffer and 72h incubation. Released amounts of drug from ME formulation were significantly enhanced compared to drug suspension group (p<0.05). Particularly, ITZ ME group displayed lower levels of inflammatory markers in the lung compared to ITZ suspension group after their IN administration in the HRV1B-infected mouse model (p<0.05). Developed ITZ ME formulation via IN route can be a promising candidate for the treatment of rhinovirus infection.
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Jeong-Jun
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Aeri
authors.initials: A
authors.lastname: Shim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea. Electronic address: hjko@kangwon.ac.kr.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019905:Benzyl Alcohol / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D017964:Itraconazole / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010850:Picornaviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D011092:Polyethylene Glycols / Q000737:chemistry; D012229:Rhinovirus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D013229:Stearic Acids / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D013229:Stearic Acids; D014867:Water; D017964:Itraconazole; D011092:Polyethylene Glycols; C067028:Solutol HS 15; C000515:cremophor EL; D019905:Benzyl Alcohol; D005990:Glycerol
keywords: Intranasal delivery; Itraconazole; Microemulsion; Rhinovirus; Therapy