title: Macrophage response to chitosan/poly-(γ-glutamic acid) nanoparticles carrying an anti-inflammatory drug.
abstract: The inflammatory response to biomaterials, traditionally viewed as detrimental, is nowadays considered essential for tissue repair/regeneration, being macrophages recognized as the key players in resolving inflammation. Here, the preparation of chitosan (Ch)/poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) as vehicle for a non-steroid anti-inflammatory drug, diclofenac (Df), is described and the response of primary human macrophages to this system is evaluated. Df was incorporated in Ch/γ-PGA NPs at controlled pH (5.0) (maximum 0.05 mg/ml). The components molar ratio and order of addition revealed to be critical to obtain NPs (315 ± 50 nm with 0.36 ± 0.06 polydispersion index). Df was released at physiological pH and this drug-delivery system was proved to be non toxic to macrophages, being rapidly internalized (95 %). Importantly, efficacy of Df-NPs was confirmed by their ability of inhibit/revert PGE2 production of activated macrophages. Therefore, Df-NPs could contribute to stifle local inflammatory reactions, namely those associated with biomaterials.
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, raquelg@ineb.up.pt.
authors: Raquel Madeira
authors: RM
authors: Gonçalves
authors: Ana Catarina Leite
authors: AC
authors: Pereira
authors: Inês Odila
authors: IO
authors: Pereira
authors: Maria José
authors: MJ
authors: Oliveira
authors: Mário Adolfo
authors: MA
authors: Barbosa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D016207:Cytokines / Q000276:immunology; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053769:Nanocapsules; C511775:poly(gamma-glutamic acid); D004008:Diclofenac; D011099:Polyglutamic Acid; D048271:Chitosan