RESUMO
Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14(+) monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14(+) monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity. From the clinical editor: The authors here fabricated hydrogel nanorods using the PRINT (Particle Replication In Nonwetting Templates) fabrication process. They tested the interaction of human immune cells with these particles and found no immunoreactivity. This finding would suggest that monodisperse PRINT particles of identical shape and size could serve a variety of clinical applications.
Assuntos
Sistemas de Liberação de Medicamentos , Imunidade Inata , Imunização/métodos , Monócitos/imunologia , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Citocinas/imunologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Receptores de Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Monócitos/citologia , Vacinas/química , Vacinas/farmacologiaRESUMO
AIDS caused by HIV-1, is a major threat to human being. An anti-HIV formulation from Chinese herbs, so called "Qu Du Zeng Ning", have been recently developed. In this work, the pharmacodynamics of the formulation in vitro was studied. The results showed that Qu Du Zeng Ning inhibit the replication of HIV-1 efficiently in all cell-based assay, with IC50 at 105.2, 70.7, 77.4 microg mL(-1), separately. A significant synergy between the formulation and zidovudine (AZT) was observed, and it also showed a potent activity against HIV-1 drug-resistant mutant.