title: Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine.
abstract: Porous poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles were tested for pulmonary delivery of hepatitis B vaccine. In particular, the effects of particle size and hydrophobicity on mucosal and cell-mediated immune responses were investigated. Three formulations of PLA and PLGA nanoparticles containing a fixed amount of hepatitis B surface antigen (HBsAg) were prepared by a double-emulsion-solvent-evaporation method and characterized for surface morphology, charge, size, density and in vitro release. The immune responses were studied by measuring secretory IgA levels in mucosal fluids and quantitating cytokine levels in rat spleen homogenates. Particle uptake was studied in rat alveolar macrophages. Scanning electron microscopy revealed particles with smooth surfaces. Zeta potential measurements indicated that the particles carried negative surface charges. The antigen was continuously released for 42 days in phosphate buffer. Hydrophobic particles >500 nm elicited a more robust increase in secretary IgA, interleukin-2 and interferon-γ levels compared to hydrophilic particles <500 nm. Large hydrophobic particles were more efficiently internalized by rat alveolar macrophages compared to smaller hydrophilic particles. Calu-3 cell viability studies indicate that the viability of cells is not affected by nanoparticulate formulations. This study demonstrates that inhalable nanoparticles of HBsAg produce an enhancement of immune responses.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, Texas 79106, USA.
authors.forename: Chandan
authors.initials: C
authors.lastname: Thomas
authors.forename: Amit
authors.initials: A
authors.lastname: Rawat
authors.forename: Louisa
authors.initials: L
authors.lastname: Hope-Weeks
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004337:Drug Carriers; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008863:Microspheres; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007071:Immunoglobulin A, Secretory; D007376:Interleukin-2; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D007371:Interferon-gamma