The environmental pollutant, polychlorinated biphenyls, and cardiovascular disease: a potential target for antioxidant nanotherapeutics.

Despite production having stopped in the 1970s, polychlorinated biphenyls (PCBs) represent persistent organic pollutants that continue to pose a serious human health risk. Exposure to PCBs has been linked to chronic inflammatory diseases, such as cardiovascular disease, type 2 diabetes, obesity, as well as hepatic disorders, endocrine dysfunction, neurological deficits, and many others. This is further complicated by the PCB's strong hydrophobicity, resulting in their ability to accumulate up the food chain and to be stored in fat deposits. This means that completely avoiding exposure is not possible, thus requiring the need to develop intervention strategies that can mitigate disease risks associated with exposure to PCBs. Currently, there is excitement in the use of nutritional compounds as a way of inhibiting the inflammation associated with PCBs, yet the suboptimal delivery and pharmacology of these compounds may not be sufficient in more acute exposures. In this review, we discuss the current state of knowledge of PCB toxicity and some of the antioxidant and anti-inflammatory nanocarrier systems that may be useful as an enhanced treatment modality for reducing PCB toxicity.

Multifunctional poly(ß-amino ester) hydrogel microparticles in periodontal in situ forming drug delivery systems.

In situ forming implants (ISIs) formed from poly(lactic-co-glycolic acid) (PLGA) have been commercialized for local drug delivery to treat periodontitis, but drug release from these bulk materials is typically subject to an initial burst. In addition, PLGA has inferior material properties for the dynamic mechanical environment of gingival tissue. In this work, poly(ß-amino ester) (PBAE) hydrogel microparticles were incorporated into a PLGA matrix to provide several new functions: mechanical support, porosity, space-filling, and controlled co-delivery of antimicrobial and osteogenic drugs. First, the effects of PBAE microparticles on ISI architecture and material properties throughout degradation were investigated. Second, the influence of PBAE microparticles on drug release kinetics was quantified. Over a 15 d period, ISIs containing PBAE microparticles possessed greater porosity, ranging from 42-80%, compared to controls, which ranged from 24-54% (p < 0.001), and these ISIs also developed significantly greater accessible volume to simulated cell-sized spheres after 5 d or more of degradation (p < 0.001). PBAE-containing ISIs possessed a more uniform microarchitecture, which preserved mechanical resilience after cyclical loading (p < 0.001), and the materials swelled to fill the injected space, which significantly increased interfacial strength in an artificial periodontal pocket (p < 0.0001). PBAE microparticles eliminated the burst of freely-mixed simvastatin compared to 36% burst from controls (p < 0.0001), and high-dose doxycycline release was prolonged from 2 d to 7 d by pre-loading drug into the microparticles. PBAE-containing PLGA ISIs are more effective space-filling scaffolds and offer improved release kinetics compared to existing ISIs used to treat periodontitis.

Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer.

Pulmonary inhalation chemotherapeutic drug delivery offers many advantages for lung cancer patients in comparison to conventional systemic chemotherapy. Inhalable particles are advantageous in their ability to deliver drug deep in the lung by utilizing optimally sized particles and higher local drug dose delivery. In this work, spray-dried and co-spray dried inhalable lung surfactant-mimic PEGylated lipopolymers as microparticulate/nanoparticulate dry powders containing paclitaxel were rationally designed via organic solution advanced spray drying (no water) in closed-mode from dilute concentration feed solution. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) with varying PEG chain length were mixed with varying amounts of paclitaxel in methanol to produce co-spray dried microparticles and nanoparticles. Scanning electron microscopy showed the spherical particle morphology of the inhalable particles. Thermal analysis and X-ray powder diffraction confirmed the retention of the phospholipid bilayer structure in the solid-state following spray drying, the degree of solid-state molecular order, and solid-state phase transition behavior. The residual water content of the particles was very low as quantified analytically Karl Fisher titration. The amount of paclitaxel loaded into the particles was quantified which indicated high encapsulation efficiencies (43-99%). Dry powder aerosol dispersion performance was measured in vitro using the Next Generation Impactor (NGI) coupled with the Handihaler dry powder inhaler device and showed mass median aerodynamic diameters in the range of 3.4-7 µm. These results demonstrate that this novel microparticulate/nanoparticulate chemotherapeutic PEGylated phospholipid dry powder inhalation aerosol platform has great potential in lung cancer drug delivery.

Hydrogel nanocomposites as remote-controlled biomaterials.

Nanocomposite hydrogels are a new class of intelligent materials which have recently attracted interest as biomaterials. In this study, magnetic nanocomposites of temperature-sensitive hydrogels have been developed and demonstrated to be responsive to alternating magnetic fields. Nanocomposites were synthesized by incorporation of superparamagnetic Fe(3)O(4) particles in negative temperature-sensitive poly(N-isopropylacrylamide) hydrogels. The systems were characterized for temperature-responsive swelling, remote heating on application of an alternating magnetic field and remote-controlled drug delivery applications. The rise in temperature in external alternating magnetic field depends on the Fe(3)O(4) particle loading of the system. Preliminary studies on remote-controlled drug release showed reduced release in the presence of an alternating magnetic field.