Sustained and specific in vitro inhibition of HIV-1 replication by a protease inhibitor encapsulated in gp120-targeted liposomes
| Autor: | Olivia Goethals, Alfred M. Del Vecchio, Francois Nicol, Kurt Hertogs, Yuan Peng Zhang, Zheng Xu, Lester L. Gutshall, Tim Hugo Maria Jonckers, Reginald Clayton, Robert T. Sarisky, Asa Ohagen, Lieve Emma Jan Michiels, Sharon Bola, Haiyan Jiang, Marnix Van Loock, John Grigsby, Mark W. Cunningham |
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| Rok vydání: | 2009 |
| Předmět: |
Drug
Anti-HIV Agents medicine.drug_class T-Lymphocytes medicine.medical_treatment media_common.quotation_subject HIV Infections HIV Envelope Protein gp120 Pharmacology Biology Virus Replication Monoclonal antibody Cell Line Polyethylene Glycols Targeted therapy Virology Immunoliposome medicine Humans Protease inhibitor (pharmacology) media_common Drug Carriers Liposome HIV Protease Inhibitors Targeted drug delivery Liposomes Drug delivery HIV-1 |
| Zdroj: | Antiviral Research. 84:142-149 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/j.antiviral.2009.08.003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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