title: Intracellular drug delivery in Leishmania-infected macrophages: Evaluation of saponin-loaded PLGA nanoparticles.
abstract: Drug delivery systems present an opportunity to potentiate the therapeutic effect of antileishmanial drugs. Colloidal carriers are rapidly cleared by the phagocytic cells of the reticuloendothelial system (RES), rendering them ideal vehicles for passive targeting of antileishmanials. This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the antileishmanial saponin β-aescin. NPs were prepared using the combined emulsification solvent evaporation/salting-out technique. Confocal microscopy was used to visualise the internalisation and intracellular trafficking of fluorescein- and nile red-labelled PLGA NPs in J774A.1 macrophages infected with GFP-transfected Leishmania donovani. The in vitro activity of aescin and aescin-loaded NPs on L. infantum was determined in the axenic model as well as in the ex vivo model. The developed PLGA NPs were monodispersed with Z(ave)<300 nm, exhibited negative zeta potentials and had relatively high drug loadings ranging from 5.80 to 8.68% w/w PLGA. The fluorescent NPs were internalised by the macrophages and trafficked towards the lysosomes after 2 h in vitro incubation. Co-localisation of the NPs and the parasite was not shown. A two-fold increase in activity was observed in the ex vivo macrophage model by encapsulating β-aescin in PLGA NPs (IC(50), 0.48-0.76 µg/mL vs. 1.55 ± 0.32 µg/mL for the free drug).
authors.affiliation: University of Antwerp, Laboratory of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Universiteitsplein 1, CDE, Antwerpen (Wilrijk), 2610 Belgium. helene.vandeven@ua.ac.be
authors.forename: H
authors.initials: H
authors.lastname: Van de Ven
authors.forename: M
authors.initials: M
authors.lastname: Vermeersch
authors.forename: R E
authors.initials: RE
authors.lastname: Vandenbroucke
authors.forename: A
authors.initials: A
authors.lastname: Matheeussen
authors.forename: S
authors.initials: S
authors.lastname: Apers
authors.forename: W
authors.initials: W
authors.lastname: Weyenberg
authors.forename: S C
authors.initials: SC
authors.lastname: De Smedt
authors.forename: P
authors.initials: P
authors.lastname: Cos
authors.forename: L
authors.initials: L
authors.lastname: Maes
authors.forename: A
authors.initials: A
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D004928:Escin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry*; D018314:Leishmania infantum / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000706:statistics & numerical data; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004928:Escin