<p>Pulmonary toxicities from a 90-day chronic inhalation study with carbon black nanoparticles in rats related to the systemical immune effects</p>

Abstract

Background: Recent years, there occurs heavy haze pollution in northern China during wintertime. The potential influence of airborne particulate matter (PM) on human health attracts great concern. The fuel-derived PM in the inhalable size range is dominated by aggregates of nanoparticles of Carbon black (CB). However, there are still lack of evidences especially regarding long-term exposure to explain the chronic effects of nanoscaled CB and the relative mechanism. Purpose: The objective of this study was to identify the potential mechanism of chronic effects of nanoscale CB. The systemic toxicity, immune suppression or activity and local toxicity were evaluated. Methods: 32 rats were divided into 2 groups: 30 mg/m3 CB exposure (nose only, 90 d, 6h/d) and control (clean air). Half of rats were scarified after exposure and another half of rats recovered for 14 days. Eight rats in each group were executed the lung function tests using a ventilated bias flow whole body plethysmograph (WBP). SDS-PAGE protocol was used to detect the deposition and retention of CB in lung of rats. HE staining was used to observe the changes of histopathology. Cell apoptosis was examined by TUNEL assay or flow cytometry. The levels of IL-6, IL-8, IL-17 and TNF-α in serum and lung tissue were evaluated with commercially available ELISA kit. The peripheral blood cell counts were detected by Auto 5-diff hematology analyzer. Results: The lung burden of CB was 16 mg in lung of rats after a 90-day exposure by MPPD. Fourteen percentages of the amount of CB accumulated at the end of the exposure period was cleared from the lung during the 14 dys recovery period. The lung function was significantly decreased and could not recover after a short time recovery. The fibroblasts and granuloma formation were found in lung. The levels of apoptosis and DNA damages were significantly increased in lung cells after CB inhalation. The cytokines levels in lung but not in serum were significantly increased in CB exposure group. The cell counts of WBC, monocytes and neutrophils had 1.72, 3.13, and 2.73-fold increases after CB exposure, respectively. The percentages of CD4+ lymphocytes and the rates of CD4+/CD8+ were statistically increased after CB exposure. The stimulation indexes of the peripheral blood lymphocytes were significantly decreased after CB exposure. In the CB exposure group, the disrupted histomorphology of thymus and spleen were found as well as the early apoptotic thymocytes had a 2.36-fold increase. Conclusion: CB induced the localized or direct toxicity and systemic immune toxicity. The direct and systemic immune responses had a combined effect on the lung damages caused by CB.

<p>Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure</p>

“…Our pilot studies, designed to explore FDNP-(NV) distribution in rat organs upon both short- and long-term exposure,7,8 demonstrated principle deposition of particles in the liver with secondary deposition to the spleen while other organs shared only a minor fraction. Interestingly, the large deposit of FDNP-(NV) in the liver 5 days after exposure remained unchanged in the 14-days and 12-weeks post-exposure studies 7,8…”

“…Our subsequent rodent POC (efficacy) studies raised an important caveat, ie, anatomical considerations suggest that recording NIR from locales within the body pose challenges associated with opacity and auto-fluorescence in an organ- and tissue-dependent manner 7. To optimize NIR signal captured from within the body in a location such as the carotid artery (in humans, 15–20 mm from skin surface), we have selected larger nanodiamond particles: FNDP-(NV)-Z-average~800 nm, a strain of particles that possess superior NIR emission (650~720 nm) over smaller particles of the same strain as well as over the NVN “color center” strain 5,6.…”

<p>Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate</p>

“…Sufficient aqueous solubility is one of the essential requirements for oral administration of a drug. Limited solubility can lead to insufficient dissolution and further reduce the bioavailability of a drug 7,8. As a result, a variety of effort has been made to enhance the oral bioavailability of poorly water soluble drugs through lipid based emulsion systems, specifically the self-emulsifying drug delivery system (SEDDS) 9–12.…”

<p>Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy</p>

“…As nanotechnology may facilitate ocular drug delivery,38,39 we constructed IL-12-PNP for the topical application and sustained release of IL-12. In addition, PLGA protects proteins against degradation and stabilizes their structure 40. We demonstrated that IL-12-PNP furnished sustained release of IL-12.…”