title: Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.
abstract: In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg.
authors: College of Life Science, Hebei Normal University, NO. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, China.
authors: Ze
authors: Z
authors: Li
authors: College of Life Science, Hebei Normal University, NO. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, China.
authors: Fangfang
authors: F
authors: Xiong
authors: College of Life Science, Hebei Normal University, NO. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, China. Electronic address: he_jintian@yahoo.com.
authors: Jintian
authors: J
authors: He
authors: College of Life Science, Hebei Normal University, NO. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, China.
authors: Xiaojing
authors: X
authors: Dai
authors: College of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China. Electronic address: wanggaizhen70@163.com.
authors: Gaizhen
authors: G
authors: Wang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004655:Emulsions; D011992:Endosomes / Q000737:chemistry; D005260:Female; D006018:Glycols; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008247:Lysosomes / Q000737:chemistry; D008264:Macrophages / Q000737:chemistry / Q000166:cytology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008351:Mannans / Q000737:chemistry*; D051379:Mice; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000941:Antigens; D004337:Drug Carriers; D004655:Emulsions; D006018:Glycols; D006514:Hepatitis B Surface Antigens; D008351:Mannans; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan
keywords: Antigen intracellular release; Chitosan; Intranasal vaccination; Mannan; PLGA microparticles; pH-responsive