Release of anti-inflammatory peptides from thermosensitive nanoparticles with degradable cross-links suppresses pro-inflammatory cytokine production.
Pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N'-bis(acryloyl)cystamine) (NGPEGSS). An anti-inflammatory peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat inflammatory diseases.
Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, Indiana 47907, United States.
Scott
S
Poh
Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, Indiana 47907, United States.
Jenny B
JB
Lin
Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, Indiana 47907, United States.
Alyssa
A
Panitch
D000178:Acrylamides / Q000737:chemistry; D000476:Alkanesulfonates / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry; D006358:Hot Temperature; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000178:Acrylamides; D000476:Alkanesulfonates; D000893:Anti-Inflammatory Agents; D057846:Cell-Penetrating Peptides; D003432:Cross-Linking Reagents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; C056288:2-acrylamido-2-methylpropanesulfonate; C067295:N-isopropylacrylamide