title: Sustained and specific in vitro inhibition of HIV-1 replication by a protease inhibitor encapsulated in gp120-targeted liposomes.
abstract: Selective delivery of antiretrovirals to human immunodeficiency virus (HIV) infected cells may reduce toxicities associated with long-term highly active antiretroviral therapy (HAART), may improve therapeutic compliance and delay the emergence of resistance. We developed sterically stabilized pegylated liposomes coated with targeting ligands derived from the Fab' fragment of HIV-gp120-directed monoclonal antibody F105, and evaluated these liposomes as vehicles for targeted delivery of a novel HIV-1 protease inhibitor. We demonstrated that the immunoliposomes were selectively taken up by HIV-1-infected cells and localized intracellularly, enabling the establishment of a cytoplasmic reservoir of protease inhibitor. In antiviral experiments, the drug delivered by the immunoliposomes showed greater and longer antiviral activity than comparable concentrations of free drug or drug encapsulated in non-targeted liposomes. In conclusion, by combining a targeting moiety with drug-loaded liposomes, efficient and specific uptake by non-phagocytic HIV-infected cells was facilitated, resulting in drug delivery to infected cells. This approach to targeted delivery of antiretroviral compounds may enable the design of drug regimens for patients that allow increased therapeutic adherence and less toxic treatment of HIV infection.
authors.affiliation: Tibotec BVBA, Generaal De Wittelaan L 11B 3, Mechelen, Belgium. rclayton@its.jnj.com
authors.forename: Reginald
authors.initials: R
authors.lastname: Clayton
authors.forename: Asa
authors.initials: A
authors.lastname: Ohagen
authors.forename: Francois
authors.initials: F
authors.lastname: Nicol
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Del Vecchio
authors.forename: Tim H M
authors.initials: TH
authors.lastname: Jonckers
authors.forename: Olivia
authors.initials: O
authors.lastname: Goethals
authors.forename: Marnix
authors.initials: M
authors.lastname: Van Loock
authors.forename: Lieve
authors.initials: L
authors.lastname: Michiels
authors.forename: John
authors.initials: J
authors.lastname: Grigsby
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Yuan Peng
authors.initials: YP
authors.lastname: Zhang
authors.forename: Lester L
authors.initials: LL
authors.lastname: Gutshall
authors.forename: Mark
authors.initials: M
authors.lastname: Cunningham
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Sharon
authors.initials: S
authors.lastname: Bola
authors.forename: Robert T
authors.initials: RT
authors.lastname: Sarisky
authors.forename: Kurt
authors.initials: K
authors.lastname: Hertogs
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D004337:Drug Carriers / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; D008081:Liposomes; D011092:Polyethylene Glycols