title: PLGA nanoparticles loaded with the antileishmanial saponin β-aescin: factor influence study and in vitro efficacy evaluation.
abstract: Colloidal carriers are known to improve the therapeutic index of the conventional drugs in the treatment of visceral leishmaniasis (VL) by decreasing their toxicity whilst maintaining or increasing therapeutic efficacy. This paper describes the development of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the antileishmanial saponin β-aescin. NPs were prepared by the W/O/W emulsification solvent evaporation technique and the influence of five preparation parameters on the NPs' size (Z(ave)), zeta potential and entrapment efficiency (EE%) was investigated using a 2(5-2) fractional factorial design. Cytotoxicity of aescin, aescin-loaded and blank PLGA NPs was evaluated in J774 macrophages and non-phagocytic MRC-5 cells, whereas antileishmanial activity was determined in the Leishmania infantum ex vivo model. The developed PLGA NPs were monodispersed with Z(ave)<500 nm and exhibited negative zeta potentials. The process variables 'surfactant primary emulsion', 'concentration aescin' and 'solvent evaporation rate' had a positive effect on EE%. Addition of Tween 80 to the inner aqueous phase rendered the primary emulsion more stable, which in its turn led to better saponin entrapment. The selectivity index (SI) towards the supporting host macrophages increased from 4 to 18 by treating the cells with aescin-loaded NPs instead of free β-aescin. In conclusion, the in vitro results confirmed our hypothesis.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerpen, 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: A
authors.initials: A
authors.lastname: Matheeussen
authors.forename: J
authors.initials: J
authors.lastname: Vandervoort
authors.forename: W
authors.initials: W
authors.lastname: Weyenberg
authors.forename: S
authors.initials: S
authors.lastname: Apers
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; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004928:Escin / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D005612:Freeze Drying; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology; D008647:Mesocricetus; D051379:Mice; D015233:Models, Statistical; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D012997:Solvents; D013501:Surface-Active Agents; D014344:Trypanocidal Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004928:Escin