Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs.

The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic⁻co⁻glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs⁻DNA⁻CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%⁻15%) after 24 h of incubation and increase in autophagy, induced by NPs⁻DNA⁻CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs⁻DNA⁻CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs.

Lamstatin--a novel inhibitor of lymphangiogenesis derived from collagen IV.

The lymphatic system is essential for the maintenance of tissue homeostasis and immunity. Its dysfunction in disease (such as lymphangioleiomyomatosis) can lead to chylous effusions, oedema or dissemination of malignant cells. Collagen IV has six α chains, of which some of the non-collagenous-1 domains have endogenous anti-angiogenic properties, however, little is known about specific endogenous anti-lymphangiogenic characteristics. In this study we sought to investigate the expression levels of collagen IV non-collagenous-1 domains in lung tissue of patients with and without lymphangioleiomyomatosis to explore the hypothesis that a member of the collagen IV family, specifically the non-collagenous domain-1 of α5, which we named lamstatin, has anti-lymphangiogenic properties. Levels of lamstatin detected by immunohistochemistry were decreased in lungs of lymphangioleiomyomatosis patients. We produced recombinant lamstatin in an E.coli expression system and synthesized a 17-amino acid peptide from a theoretically identified, active region (CP17) and tested their effects in vitro and in vivo. Recombinant lamstatin and CP17 inhibited proliferation, migration and cord formation of human microvascular lung lymphatic endothelial cells, in vitro. Furthermore, lamstatin and CP17 decreased complexity and dysplasia of the tumour-associated lymphatic network in a lung adenocarcinoma xenograft mouse model. In this study we identified a novel, direct inhibitor of lymphangiogenesis, derived from collagen IV. This may prove useful for exploring new avenues of treatment for lymphangioleiomyomatosis and metastasis via the lymphatic system in general.

Interaction of water with three granular biopesticide formulations.

Two obstacles for biopesticide commercialization, long shelf life and reliable efficacy, are both affected by moisture availability. Three biopesticide delivery systems, TRE-G, PEC-G, and PESTA, were analyzed by dynamic vapor sorption analysis. The objective was to investigate the moisture sorption profile of each system in air at 25 degrees C and a relative humidity (RH) ranging from 0 to 90%. The formulations sorbed up to 12.7% moisture. In rehydrating from 0.00 to 90% RH, TRE-G and PEC-G were >or=63% and >or=58% faster than Pesta, respectively. In losing moisture from 90 to 0.00% RH, Pesta was 3.4 and 2.3 times slower than TRE-G and PEC-G, respectively. The GAB model was inadequate for describing moisture sorption, but the Young and Nelson model showed good correlation (r > 0.990) for all three formulations. Moisture distribution for all formulations was obtained. The implications of the findings as they relate to shelf life and dew period requirements of biopesticides are discussed.

Efficacy of bait supplements for improving the rate of discovery of bait stations in the field by formosan subterranean termites (Isoptera: Rhinotermitidae).

Field tests of four different bait supplements were conducted in City Park, New Orleans, LA. The four bait supplements tested included two different formulations of decayed material, a sports drink, and the combination of an application of an aqueous solution of Summon Preferred Food Source disks with the disk itself. Although all the bait supplements in this study resulted in a slightly greater number of treated stations discovered compared with control stations, only the application of the aqueous solution combined with the disk caused a significant increase in the number of stations discovered by termites. This treatment resulted in a significantly greater rate of discovery of treated stations versus control stations after only 14 d in the field. Termites were able to discover six times as many treated as control stations after 14 d, 9 times as many after 28 d, and 12 times as many after 42 d. These findings provide evidence that the diffusion of an aqueous solution into the soil underneath monitoring stations significantly decreased the length of time required for termites to infest stations.