title: Rational design of solid aerosols for immunoglobulin delivery by modulation of aerodynamic and release characteristics.
abstract: Parenteral administration of immunoglobulins (Ig) for prevention or treatment of respiratory diseases achieves only modest concentrations of antibody in the pulmonary interstitial tissue and airways. Aerosols, including spray-dried particles, must overcome two limiting factors in order to be effective vehicles for pulmonary delivery of Ig: (i) Fc receptor (FcR)-mediated scavenging by macrophages and (ii) clearance by the mucociliary system. Ig-incorporated spray-dried lipid microparticles (SDLM), coformulated with or without a biocompatible surfactant (1% w:w) to modulate protein release, were designed and tested for their capability to deliver Ig to the respiratory tract. To determine efficacy, rodents were immunized with SDLM containing antiinfluenza antibody followed by virus challenge and clinical parameters measured. Control of the release kinetics resulted in enhanced delivery of immunoglobulins to the respiratory tract and interstitial tissue with slow translocation into the systemic circulation. As much as 60% of the IgG delivered from nonretentive SDLM could be recovered from the lung interstitial tissue within 1 h after aerosol administration at a dose of 1 mg of Ig/kg of body weight. In addition, nonretentive rather than slow-release particles loaded with antiinfluenza antibody were effective in curbing virus replication with a resulting positive clinical outcome. Thus, controlled release of Ig by manipulating aerosol characteristics and composition allows for a significant increase in the efficiency of pulmonary delivery of antibodies.
authors.affiliation: Department of Immunology, Alliance Pharmaceutical Corp. San Diego, CA 92121, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Dellamary
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Smith
authors.forename: Amy
authors.initials: A
authors.lastname: Bloom
authors.forename: Simona
authors.initials: S
authors.lastname: Bot
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Guo
authors.forename: Hemant
authors.initials: H
authors.lastname: Deshmuk
authors.forename: Michael
authors.initials: M
authors.lastname: Costello
authors.forename: Adrian
authors.initials: A
authors.lastname: Bot
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry / Q000493:pharmacokinetics; D007074:Immunoglobulin G / Q000008:administration & dosage*; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009330:Nebulizers and Vaporizers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical
chemical_list: D000336:Aerosols; D001672:Biocompatible Materials; D004337:Drug Carriers; D005466:Fluorocarbons; D007074:Immunoglobulin G