Thermosensitive Nanoparticles with pH-Triggered Degradation and Release of Anti-inflammatory Cell-Penetrating Peptides

• Published in: Biomacromolecules Vol. 13; no. 8; pp. 2578 - 2584
• Main Authors: Bartlett, Rush L, Panitch, Alyssa
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 13.08.2012
• Subjects: Acrylamides - chemistry; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Applied sciences; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - pharmacology; Cross-Linking Reagents - chemistry; Exact sciences and technology; Humans; Hydrogen-Ion Concentration; Hydrolysis; Hydroxylamines - chemistry; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Investigative techniques, diagnostic techniques (general aspects); Lipopolysaccharides - pharmacology; Medical sciences; Miscellaneous. Technology; Nanocapsules - chemistry; Nanocapsules - toxicity; Nanocapsules - ultrastructure; Organic polymers; Particle Size; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Physicochemistry of polymers; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Temperature; Tumor Necrosis Factor-alpha - metabolism; Biological properties; Fluorescence; Cytotoxicity; Nanoencapsulation; Lateral group; Spiran copolymer; Chain transfer; Radiation effect; Amine copolymer; Amphiphilic polymer; Aldose; Photoisomerization; Branched copolymer; Dithioester; Experimental study; In vitro; Hela cell line; Absorption spectrum; Polyelectrolyte; Free radical polymerization; Resonant energy transfer; Internalization; Preparation; Light sensitive copolymer; Indole derivative copolymer; Methacrylate copolymer; Aqueous solution; Fluorescent compound; Micellar solution; Block copolymer
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm300826v

Poly(N-isopropylacrylamide–2-acrylamido-2-methyl-1-propanesulfonate) [poly(NIPAm–AMPS)] nanoparticles can be cross-linked with hydrolytically degradable N,O-dimethacryloyl hydroxylamine (DMHA) in order to yield a pH-sensitive drug delivery system that slowly erodes above pH 5.0. Varying the composition of degradable DMHA and nondegradable MBA cross-linking allows for engineered variation of particle size and degradation kinetics. Utilizing sulfated comonomer AMPS provides for increased passive loading of anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide KAFAKLAARLYRKALARQLGVAA (KAFAK) between 24.3% and 29.2% (w/w) for nanoparticles with 5 mol % cross-linker. Nanoparticles were shown to be nontoxic in vitro and were effective at delivering a therapeutically active dose of KAFAK to THP1 human monocytes to suppress tumor necrosis factor α (TNF-α) expression during lipopolysaccharide (LPS)-induced inflammation. This thermosensitive nanoparticle system is an excellent platform for passive diffusive loading in deionized water and release in physiologically relevant ionic strength media of environmentally sensitive peptide therapeutics.