Human Granulocyte Macrophage Colony-Stimulating Factor Enhances Antibiotic Susceptibility of Pseudomonas aeruginosa Persister Cells.

Bacterial persister cells are highly tolerant to antibiotics and cause chronic infections. However, little is known about the interaction between host immune systems with this subpopulation of metabolically inactive cells, and direct effects of host immune factors (in the absence of immune cells) on persister cells have not been studied. Here we report that human granulocyte macrophage-colony stimulating factor (GM-CSF) can sensitize the persister cells of Pseudomonas aeruginosa PAO1 and PDO300 to multiple antibiotics including ciprofloxacin, tobramycin, tetracycline, and gentamicin.

Investigation of the cytokine response to NF-κB decoy oligonucleotide coated polysaccharide based nanoparticles in rheumatoid arthritis in vitro models.

Introduction: The transcription factor nuclear factor-kappa B (NF-κB) is highly involved in regulation of a number of cellular processes, including production of inflammatory mediators. Thus, this transcription factor plays a role in pathology of many diseases, including rheumatoid arthritis, an autoimmune disease hallmarked by an imbalance of pro and anti-inflammatory cytokines. Small nucleic acids with sequences that mimic the native binding site of NF-κB have been proposed as treatment options for RA; however due to low cellular penetration and a high degree of instability, clinical applications of these therapeutics have been limited.

Immunomodulation of cystic fibrosis epithelial cells via NF-κB decoy oligonucleotide-coated polysaccharide nanoparticles.

Activation of the transcription factor nuclear factor-kappa B (NF-κB) signaling pathway is associated with enhanced secretion of pro-inflammatory mediators and is thought to play a critical role in diseases hallmarked by inflammation, including cystic fibrosis (CF). Small nucleic acids that interfere with gene expression have been proposed as promising therapeutics for a number of diseases. However, applications have been limited by low cellular penetration and a lack of stability.

In vitro efficacy of polysaccharide-based nanoparticles containing disease-modifying antirheumatic drugs.

Purpose: To evaluate the therapeutic efficacy of dexamethasone (DM) and methotrexate (MTX) entrapped within polysialic acid (PSA)-trimethyl chitosan (TMC) nanoparticles using an in vitro model of rheumatoid arthritis (RA).

Methods: The loading capacity of the PSA-TMC nanoparticles was determined. An RA in vitro model was developed by stimulating a synovial cell line with a proinflammatory mediator.

Polysaccharide-based micelles for drug delivery.

Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems.

Synthesis and evaluation of cyclosporine A-loaded polysialic acid-polycaprolactone micelles for rheumatoid arthritis.

Polysialic acid (PSA) has been identified as a natural, hydrophilic polymer that can be used to extend circulation time and improve therapeutic efficacy when used as the basis of drug carrier systems. Here, to further investigate the potential of PSA to alter the pharmacokinetic and pharmacodynamic profiles of associated therapeutics, PSA-based micelles were formed via self-assembly of PSA grafted with polycaprolactone (PCL) at a critical micelle concentration of 84.7±13.

PMMA brush-containing two-solution bone cement: preparation, characterization, and influence of composition on cement properties.

Two-solution bone cement consisting of poly (methyl methacrylate) (PMMA) brushes in methyl methacrylate has been developed as an alternative to the traditional two-solution (TSBC) and powder-liquid cements. It was hypothesized that the substitution of brushes, for the entire pre-polymer phase of the cement, would permit a decrease in solution viscosity at higher polymer fractions, and allow for physical entanglements with the cement matrix. Consequently, improved cement exothermal and mechanical properties could be expected with brush addition.

Polysialic acid-based micelles for encapsulation of hydrophobic drugs.

Despite improvements relative to unmodified counterparts, poly(ethylene glycol) (PEG) conjugation may not be the ideal solution for improving circulatory stability of current nanoparticle carriers or free drugs. Polysialic acid (PSA), a natural polymer for which the body possesses no receptors, has been conjugated directly to biologically active molecules to prevent premature clearance; however, this concept has not yet been applied to nanoparticle drug carrier systems. In the current study, PSA was modified with a long-chain hydrocarbon through reaction of the carboxylic acid side groups with N-decylamine (DA).

Modulation of the keratinocyte-fibroblast paracrine relationship with gelatin-based semi-interpenetrating networks containing bioactive factors for wound repair.

Gelatin-based semi-interpenetrating networks (sIPNs) containing soluble and covalently-linked bioactive factors have been shown to aid in wound healing; however, the biological responses elicited by the introduction of sIPN biomaterials remain unclear. In the current study, modulation of the re-epithelialization phase of wound healing by sIPNs grafted with PEGylated fibronectin-derived peptides and utilized as platforms for the delivery of exogenous keratinocyte growth factor (KGF) was evaluated. Following wounding, keratinocyte migration, proliferation and protein secretion is largely controlled by diffusible factors, such as KGF, released by the underlying fibroblasts.

A study of diffusion in poly(ethyleneglycol)-gelatin based semi-interpenetrating networks for use in wound healing.

Semi-interpenetrating networks (sIPNs) designed to mimic extracellular matrix via covalent crosslinking of poly(ethylene glycol) diacrylate in the presence of gelatin have been shown to aid in wound healing, particularly when loaded with soluble factors. Ideal systems for tissue repair permit an effective release of therapeutic agents and flow of nutrients to proliferating cells. Appropriate network characterization can, consequently, be used to convey an understanding of the mass transfer kinetics necessary for materials to aid in the wound healing process.

Concurrent in vitro release of silver sulfadiazine and bupivacaine from semi-interpenetrating networks for wound management.

In situ photopolymerized semi-interpenetrating networks (sIPNs) composed of poly(ethylene glycol) and gelatin are promising multifunctional matrices for a regenerative medicine approach to dermal wound treatment. In addition to previously demonstrated efficacy in critical defects, sIPNs also function as drug delivery matrices for compounds loaded as either soluble or covalently linked components. Simultaneous release of silver sulfadiazine and bupivacaine from the sIPN would provide multiple-hit management of dermal wounds that minimizes infection, and manages pain along with sIPN absorption of exudates and facilitation of epidermal regrowth.

Synthesis and viscoelastic characterization of novel hydrogels generated via photopolymerization of 1,2-epoxy-5-hexene modified poly(vinyl alcohol) for use in tissue replacement.

Hydrogels have been proposed as candidates for tissue replacement; however, current systems are often highly susceptible to hydrolytic degradation and have not been shown to mimic the viscoelastic behavior of the native tissue when subjected to dynamic loading conditions. In the present work, 1,2-epoxy-5-hexene modified poly(vinyl alcohol) was crosslinked via photopolymerization to generate non-degradable hydrogels with mechanical properties and network characteristics that could be modulated through variation in the type and percentage of a monomeric additive. Complex shear moduli obtained from dynamic frequency sweeps in torsional shear were used to exemplify the differences in the viscoelastic behavior of the materials, and the corresponding changes in crosslink density were determined by rubber elasticity theory.

Rheological characterization of photopolymerized poly(vinyl alcohol) hydrogels for potential use in nucleus pulposus replacement.

Hydrogels have been proposed as candidates for nucleus pulposus replacement because of their similarity in mechanical behavior to the native tissue when subjected to transient or static loading; however, given the viscoelastic nature of soft biological tissues, the lack of dynamic testing is a significant inadequacy in the studies performed to date. In the present work, the viscoelastic behavior of a hydrogel system obtained via photopolymerization of glycidyl methacrylate modified poly(vinyl alcohol) (PVA) was evaluated in comparison to that of the nucleus pulposus when subjected to dynamic torsional shear. The complex shear moduli and phase shift angles were modulated through the variation of PVA molecular weight and concentration of polymer prior to photopolymerization.