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1.
Int J Biol Macromol ; 227: 576-589, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549613

RESUMO

Nanoparticles targeting the DEC-205 receptor were found to induce antigen-specific protective immune response. When the delivery system carries both antigens and immunomodulators, it can maximize the expected therapeutic effect of the drug and induce effective humoral and cellular immune responses to antigens.In this study, we encapsulated the Eucommia ulmoides Oliv. polysaccharides (EUPS) into PLGA nanoparticles (NPs) and conjugated it with anti-CD205 monoclonal Ab (MAb) to produce a DEC-205 receptor targeted PLGA nanoparticles (anti-DEC-205-EUPS-PLGA NPs). The physicochemical characteristics and adjuvant activity of the above NPs were evaluated in vitro and in vivo. In the in vitro setting, 200 µg·mL-1 anti-DEC-205-EUPS-PLGA could improve the proliferation of DCs and promote their antigen up-take activity. In the in vivo setting, anti-DEC-205-EUPS-PLGA NPs remarkably controlled the release of drug and antigen to induce sustained immune responses and up-regulated the levels of FMDV-specific IgG antibodies, promoted the cytotoxic activity of CTLs and NK cells, and improved the proliferation of splenocytes. Moreover, the anti-DEC-205-EUPS-PLGA NPs facilitated the maturation of DCs. The above data indicated that anti-DEC-205-EUPS-PLGA NPs employed as an targeted adjuvant induced the humoral and cellular immune activity by promoting the maturation of DCs. These findings may provide a new insight onto the development of vaccine adjuvants.


Assuntos
Eucommiaceae , Febre Aftosa , Nanopartículas , Vacinas , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Glicóis , Células Dendríticas , Antígenos , Imunidade Celular , Adjuvantes Imunológicos/farmacologia , Polissacarídeos/farmacologia
2.
Int J Biol Macromol ; 224: 998-1011, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306904

RESUMO

Potentilla anserina L polysaccharide (PAP) is known to regulate immunity. Poly(lactic-co-glycolicacid) (PLGA) is a type of drug carrier with biocompatibility and biodegradable USFDA approved polymer, which possesses the advantages of high safety and good sustained-release effect. The DEC205 receptor, a type I membrane protein, is widely distributed on the surface of macrophages and dendritic cells (DCs) and plays a key role in antigen recognition and presentation. In this study, we prepared Potentilla anserina L polysaccharide PLGA nanoparticles targeting DEC205 receptor (DEC205-PAPP) and characterized the nanoparticles with regards to their effects on immune activation in vitro and in vivo. In vitro, DEC205-PAPP promoted the uptake activity of macrophages and increased the secretion of NO and cytokines (IFN-γ, IL-4, IL-6, and GM-CSF), up-regulated the expression of CD80+, CD86+. In vivo, DEC205-PAPP elevated the immune organ index, induced DC maturation, promoted T lymphocyte proliferation and differentiation, and increased the levels of antigen-specific IgG antibody and cytokines (IFN-γ, IL-4), which prolonged the residence time of the OVA antigen in the immune organs and the lymph nodes. In conclusion, DEC205-PAPP had a slow-release effect, induced humoral and cellular immune responses, and could potentially be used as an effective antigen-targeted delivery system.


Assuntos
Nanopartículas , Potentilla , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Interleucina-4/metabolismo , Antígenos , Imunidade Celular , Citocinas/metabolismo , Nanopartículas/química , Polissacarídeos/química , Células Dendríticas
3.
Int Immunopharmacol ; 119: 110242, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37126987

RESUMO

CD-205 receptor-mediated dendritic cell (DC) targeting liposomes are commonly used as a delivery system for inducing a strong T-cell immune response or specific immune tolerance. This delivery system can carry both the antigen and adjuvant, thereby modulating DC maturation and also activating the T-cell response. In order to maximize the desired therapeutic effects of Astragalus polysaccharides (APS) and induce an efficient cellular and humoral immune response against the antigen, ovalbumin (OVA) and APS were encapsulated in long-circling liposomes conjugated with anti-CD-205 receptor antibodies to produce CD-205-targeted liposomes (iLPSM). We explored using a series of experiments evaluating the targeting efficiency of iLPSM. In vitro, iLPSM nanoparticles promoted the proliferation of macrophages, and the nanoparticles were rapidly phagocytized by macrophages. In vivo, iLPSM significantly improved the antibody titers of OVA-specific IgG and IgG, isotypes cytokine production, and T and B lymphocyte differentiation. Furthermore, iLPSM facilitated the maturation of DCs. In addition, iLPSM nanoparticles could prolong the retention time of nanoparticles at the injection site, leading to a strong, sustained immune response. These results show that the CD-205 antibody successfully binds to the corresponding cell receptor.


Assuntos
Astrágalo , Lipossomos , Lipossomos/metabolismo , Antígenos , Polissacarídeos/farmacologia , Ativação Linfocitária , Adjuvantes Imunológicos , Diferenciação Celular , Imunoglobulina G , Células Dendríticas , Ovalbumina
4.
Sci Total Environ ; 738: 139757, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32516674

RESUMO

This study systematically investigated the impact of dissolved organic matters (DOM) fractions, Ca2+, membrane orientation and real water matrix on the membrane fouling and the subsequent pharmaceutical retention in forward osmosis (FO). Ca2+ increased the removal of carbamazepine (CBZ) through steric effect, while it reduced sulfamethoxazole (SMZ) removal due to reduced electrostatic repulsion and enhanced external concentration polarization for three organic foulants. The study of operating mode showed that the pharmaceutical removal in pressure retarded osmosis (PRO) mode were lower than those in FO mode for both the baseline and HA fouling, which was attributed to the concentrative internal concentration polarization caused by long-term accumulation of pharmaceuticals or HA in support layer. In terms of the real water tests, the secondary effluent used as feed solution caused higher hydrophilicity and negative charge of fouled FO membrane, leading to increased removal of pharmaceuticals. Seawater used as draw solution also caused severe fouling in the support layer of FO with humic acid-like material as major foulants, increasing the removal of SMZ because of enhanced steric hindrance and electrostatic repulsion. However, the combined effects of increased adsorption and steric effect resulted in little change for the CBZ removal. This study gave implications on the practical application of FO process for pharmaceutical removal.


Assuntos
Purificação da Água , Membranas Artificiais , Osmose , Águas Residuárias , Água
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