三次体の格子における極小点の求め方

筑波大学 (University of Tsukuba)201

In Vitro Characterization of Inhalable Cationic Hybrid Nanoparticles as Potential Vaccine Carriers

In this study, PGA-co-PDL nanoparticles (NPs) encapsulating model antigen, bovine serum albumin (BSA), were prepared via double emulsion solvent evaporation. In addition, chitosan hydrochloride (CHL) was incorporated into the external phase of the emulsion solvent method, which resulted in surface adsorption onto the NPs to form hybrid cationic CHL NPs. The BSA encapsulated CHL NPs were encompassed into nanocomposite microcarriers (NCMPs) composed of l-leucine to produce CHL NPs/NCMPs via spray drying. The CHL NPs/NCMPs were investigated for in vitro aerosolization, release study, cell viability and uptake, and stability of protein structure. Hybrid cationic CHL NPs (CHL: 10 mg/mL) of particle size (480.2 ± 32.2 nm), charge (+14.2 ± 0.72 mV), and BSA loading (7.28 ± 1.3 µg/mg) were produced. The adsorption pattern was determined to follow the Freundlich model. Aerosolization of CHL NPs/NCMPs indicated fine particle fraction (FPF: 46.79 ± 11.21%) and mass median aerodynamic diameter (MMAD: 1.49 ± 0.29 µm). The BSA α-helical structure was maintained, after release from the CHL NPs/NCMPs, as indicated by circular dichroism. Furthermore, dendritic cells (DCs) and A549 cells showed good viability (≥70% at 2.5 mg/mL after 4–24 h exposure, respectively). Confocal microscopy and flow cytometry data showed hybrid cationic CHL NPs were successfully taken up by DCs within 1 h of incubation. The upregulation of CD40, CD86, and MHC-II cell surface markers indicated that the DCs were successfully activated by the hybrid cationic CHL NPs. These results suggest that the CHL NPs/NCMPs technology platform could potentially be used for the delivery of proteins to the lungs for immunostimulatory applications such as vaccines

Progress in mucosal immunization for protection against pneumococcal pneumonia

Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses