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Nanomedicine. 2019 Jul 31;21:102073. doi: 10.1016/j.nano.2019.102073. [Epub ahead of print]

Preferential uptake of chitosan-coated PLGA nanoparticles by primary human antigen presenting cells.

Author information

1
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
2
Department of Pharmacy, Saarland University, Saarbrücken, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Center for Infection Research (HZI) Department of Drug Delivery (DDEL), Saarbrücken, Germany.
3
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Cluster of Excellence - Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany. Electronic address: Ulrich.Kalinke@twincore.de.
4
Department of Pharmacy, Saarland University, Saarbrücken, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Center for Infection Research (HZI) Department of Drug Delivery (DDEL), Saarbrücken, Germany. Electronic address: Claus-Michael.Lehr@helmholtz-hzi.de.

Abstract

Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect of PLGA or CS-PLGA NP treatment on human peripheral blood mononuclear cells (PBMC), as well as on monocyte-derived DC (moDC). Amongst PBMC, antigen presenting cells (APC) showed higher uptake of both NP preparations than lymphocytes. Furthermore, moDC internalized CS-PLGA NP more efficiently than PLGA NP, presumably because of receptor-mediated endocytosis. Consequently, CS-PLGA NP were delivered mostly to endosomal compartments, whereas PLGA NP primarily ended up in lysosomes. Thus, CS-PLGA NP confer enhanced delivery to endosomal compartments of APC, offering new therapeutic options to either induce or modulate APC function and to inhibit pathogens that preferentially infect APC.

KEYWORDS:

Chitosan-PLGA NP; Intracellular trafficking; Monocyte-derived DC; Nanoparticles; PBMC; PLGA NP

PMID:
31376570
DOI:
10.1016/j.nano.2019.102073
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