title: In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide) microspheres.
abstract: Treatment of many intracellular infections in the mononuclear phagocytic system (MPS), requires targeting of antibiotics by a drug delivery system. The objective of this study was to examine whether the particular nature of microspheres, made of end-group capped and uncapped poly(lactide) [PLA] and poly(lactide-co-glycolide) [PLGA 50:50 and PLGA 75:25], affect the uptake into and also the activation of monocyte-macrophages. Placebo and gentamicin sulfate containing microspheres were incubated with J774 murine monocyte-macrophages and fresh human blood monocytes. Phagocytosis became more efficient with increasing polymer hydrophobicity, whereas opsonization of the particles in serum exerted inconsistent effects. Monocyte activation was determined by flow cytometry and measured as oxidative burst. The cellular oxidative burst induced by the particles was higher for end-group uncapped polymers. Opsonization increased significantly the oxidative activity of J774 monocytes, but affected inconsistently that of human blood monocytes. The results demonstrate that PLA and PLGA microspheres loaded with gentamicin sulfate were efficiently phagocytosed in vitro. The end-group uncapped polymer-type microspheres promoted significantly cell activation, which may be of importance for drug delivery and targeting to intracellular infections.
authors.affiliation: Department of Microbiology, University of Navarra, Apdo. 177, 31080 Pamplona, Navarra, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Prior
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
authors.forename: Natalia
authors.initials: N
authors.lastname: Blarer
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Merkle
authors.forename: Marija Luisa
authors.initials: ML
authors.lastname: Subirá
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Irache
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamazo
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000008:administration & dosage* / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008863:Microspheres; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D011091:Polyesters / Q000008:administration & dosage / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects; D055672:Static Electricity
chemical_list: D000617:Aminoglycosides; D001672:Biocompatible Materials; D005839:Gentamicins; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)