RESUMEN
Micelles for mucosal immunity: A mucosal vaccine system based on γ-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture).
Asunto(s)
Portadores de Fármacos/administración & dosificación , Sistemas de Liberación de Medicamentos , Inmunidad Mucosa/inmunología , Nanopartículas/administración & dosificación , Polímeros/administración & dosificación , Vacunas/administración & dosificación , Vacunas/inmunología , Administración Intranasal , Animales , Antígenos Virales/inmunología , Portadores de Fármacos/farmacocinética , Inmunidad Humoral/inmunología , Ratones , Ratones Endogámicos C57BL , Moco/efectos de los fármacos , Moco/inmunología , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Ácido Poliglutámico/análogos & derivados , Ácido Poliglutámico/química , Polímeros/farmacocinética , Distribución Tisular , VacunaciónRESUMEN
An easy but robust strategy for the synthesis of bioderived polyelectrolyte nanogels for protein antigen loading and vaccine adjuvant systems that can improve both humoral (Th2) and cellular immunity (Th1) is presented. The synthesized polyelectrolyte nanogels promote the uptake of antigens into antigen-presenting cells and strongly induce ovalbumin-specific INF-γ producing cells, cytotoxic T cell activity, and antibody production.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Presentación de Antígeno/efectos de los fármacos , Antígenos/inmunología , Materiales Biocompatibles/farmacología , Electrólitos/farmacología , Polietilenglicoles/farmacología , Polietileneimina/farmacología , Vacunas/inmunología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Ratones , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Nanogeles , Ovalbúmina/inmunología , Tamaño de la Partícula , Electricidad EstáticaRESUMEN
We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(gamma- glutamic acid) (gamma-PGA). gamma-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated gamma-PGA was synthesized by covalent coupling between the carboxyl groups of gamma-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded gamma-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated gamma-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated gamma-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked gamma-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked gamma-PGA nanogels in aqueous solution were 136.3 +/- 37.6 nm and -32.5 +/- 5.3 mV, respectively. The loading amount of Dox was approximately 38.7 microgram per mg of gamma-PGA nanogel. The Dox-loaded disulfide cross-linked gamma-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1- 10 mM). Through fluorescence microscopy and FACS, the cellular uptake of gamma-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of gamma-PGA nanogels. The bio-derived gamma-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.