Pulmonary administration of IgG loaded liposomes for passive immunoprophylaxy.
Local passive immunoprophylaxy has been used in pulmonary infectious diseases successfully. However, the short immunoglobulins half-life in the lungs limits the duration of their action. The aim of the present study was to evaluate the efficiency of human polyvalent intravenous immunoglobulins (IVIG) when protected after encapsulation within EPC: DPPG liposomes by dehydration/rehydration. Two IVIG concentrations were chosen: 10 and 1 mg/ml for further studies in mice infected by influenza A. For the highest concentration (10 mg/ml), IVIG loaded liposomes did not significantly differ from IVIG/unloaded liposomes mixture with around 45% association yield. For the lowest concentration (1 mg/ml), two thirds of the IVIG associated were found inside the vesicles. In vivo, IVIG administered intranasally at 10 mg/ml (500 microg per mouse) 4 days before the infection led to 100% survival whatever the formulation. When administered at a lower dose (1 mg/ml-50 microg per mouse) 2 days before the challenge, loaded liposomes were found less efficient than free IVIG while unloaded liposomes showed a slight aspecific immunoprotection. Gastrointestinal clearance must be responsible for a major loss of liposomes compared to IVIG solution because of a higher viscosity of the formulation. Discrepancies with the literature are discussed.
Dreffier
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C
Faculty of Pharmacy, University of Paris-Sud XI, UMR CNRS 8612, 5 Rue J-B Clément, 92296 Châtenay-Malabry Cedex, France.
Ramisse
F
F
Dubernet
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C
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005069:Evaluation Studies as Topic; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D009980:Influenza A virus / Q000187:drug effects; D007251:Influenza, Human / Q000517:prevention & control*; D008081:Liposomes / Q000378:metabolism* / Q000627:therapeutic use; D008171:Lung Diseases / Q000188:drug therapy* / Q000821:virology; D051379:Mice; D012196:Review Literature as Topic; D013997:Time Factors
D004337:Drug Carriers; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008081:Liposomes