To investigate whether vegetative endpoints are protective of reproductive endpoints in terrestrial plant risk assessments (RAs) for authorization of plant protection products (PPPs), we assessed differences in sensitivity to herbicides between these parameters. Published literature and unpublished proprietary data generated for the registration of PPPs were used to compile a database. If reproductive endpoints were systematically more sensitive than the vegetative endpoints on which regulatory decisions are presently based, a concern could be raised about the protectiveness of the current RA process.
View Article and Find Full Text PDFA comprehensive critical review was undertaken aiming to compare the intrinsic sensitivity of terrestrial plant species (crop species and noncrop wild species) with published literature and unpublished proprietary data generated for the registration of plant protection products (PPPs), and a database was compiled. Data were assessed to answer the question whether crops differ from noncrop plants in their intrinsic sensitivity to PPPs. Endpoints were assessed considering further potentially relevant parameters by means of different methods, including a quotient approach, in which overall crop endpoints were divided by matching wild species endpoints.
View Article and Find Full Text PDFUnlabelled: Antibodies that specifically bind polyethylene glycol (PEG) can lead to rapid elimination of PEGylated therapeutics from the systemic circulation. We have recently shown that virus-binding IgG can immobilize viruses in mucus via multiple low-affinity crosslinks between IgG and mucins. However, it remains unclear whether anti-PEG antibodies in mucus may also alter the penetration and consequently biodistribution of PEGylated nanoparticles delivered to mucosal surfaces.
View Article and Find Full Text PDFMucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and mucoinert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanoparticles (CP), reached the vaginal epithelial surface in vivo in mice.
View Article and Find Full Text PDFIncomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides, for preventing sexually transmitted infections. We investigated vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution.
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