Analysis of the murine immune response to pulmonary delivery of precisely fabricated nano- and microscale particles

• Published in: PloS one 2013-04, Vol.8 (4), p.e62115
• Main Authors: Roberts, Reid A, Shen, Tammy, Allen, Irving C, Hasan, Warefta, DeSimone, Joseph M, Ting, Jenny P Y
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Biocompatibility; Biodegradability; Biodegradation; Biology; Biomedical materials; Bone composition; Bone marrow; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cancer; Cell activation; Cytokines; Design; Design parameters; Drug Delivery Systems; Electronic mail systems; Fabrication; Female; Gene expression; Glycolic acid; Histopathology; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Immune clearance; Immune response; Immune system; Immunity; Immunity - drug effects; Immunology; Immunotherapy; Inflammasomes; Inflammation; Innate immunity; Lactic Acid - pharmacology; Lung - drug effects; Lung - immunology; Lungs; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Materials Science; Medical research; Medicine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Monocytes; Nanomaterials; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - ultrastructure; Nanotechnology; Particle composition; Particle Size; Particulates; Pharmacy; Physical properties; Pneumonia - pathology; Polyethylene; Polyethylene glycol; Polyethylene Glycols - pharmacology; Polyglycolic Acid - pharmacology; Polylactic Acid-Polyglycolic Acid Copolymer; Polylactide-co-glycolide; Polymers; Polyols; Shape recognition; Type 2 diabetes; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0062115

Nanomedicine has the potential to transform clinical care in the 21(st) century. However, a precise understanding of how nanomaterial design parameters such as size, shape and composition affect the mammalian immune system is a prerequisite for the realization of nanomedicine's translational promise. Herein, we make use of the recently developed Particle Replication in Non-wetting Template (PRINT) fabrication process to precisely fabricate particles across and the nano- and micro-scale with defined shapes and compositions to address the role of particle design parameters on the murine innate immune response in both in vitro and in vivo settings. We find that particles composed of either the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) or the biocompatible polymer polyethylene glycol (PEG) do not cause release of pro-inflammatory cytokines nor inflammasome activation in bone marrow-derived macrophages. When instilled into the lungs of mice, particle composition and size can augment the number and type of innate immune cells recruited to the lungs without triggering inflammatory responses as assayed by cytokine release and histopathology. Smaller particles (80×320 nm) are more readily taken up in vivo by monocytes and macrophages than larger particles (6 µm diameter), yet particles of all tested sizes remained in the lungs for up to 7 days without clearance or triggering of host immunity. These results suggest rational design of nanoparticle physical parameters can be used for sustained and localized delivery of therapeutics to the lungs.