Transcorneal Permeation in a Corneal Device of Non-Steroidal Anti-Inflammatory Drugs in Drug Delivery Systems

This work is focused on the ex vivo study of corneal permeation of two anti-inflammatory drugs: diclofenac, and flurbiprofen (as a model of hydrophilic and lipophilic drug, respectively) loaded to cyclodextrins or polymeric nanoparticles in order to determine differences in their corneal permeation against free drug or commercial eye drops. These studies were carried out in a corneal device designed and developed in our laboratory. In this work the habitual conditions for the permeation studies were modified to reproduce the behaviour when eye drops were administered. For this reason a new tetracompartmental pharmacokinetic model was developed. The complex formation of diclofenac with cyclodextrins and the flurbiprofen loaded to polymeric nanoparticles has been shown as effective procedures to remarkably increase the bioavailability of the anti-inflammatory drugs. The efficiency of polymeric nanoparticles of Poly (D-L lactic-coglycolyc) acid and poly-ε-caprolacton as intraocular targeting of NSAIDs has also been proved, being the latter polymer more effective to increase the flurbiprofen corneal permeation. The apparent corneal permeability coefficient of samples has been calculated getting a low permeation values for free drugs

Genetic diversity of peanut (Arachis hypogaea L.) and its wild relatives based on the analysis of hypervariable regions of the genome

BACKGROUND: The genus Arachis is native to a region that includes Central Brazil and neighboring countries. Little is known about the genetic variability of the Brazilian cultivated peanut (Arachis hypogaea, genome AABB) germplasm collection at the DNA level. The understanding of the genetic diversity of cultivated and wild species of peanut (Arachis spp.) is essential to develop strategies of collection, conservation and use of the germplasm in variety development. The identity of the ancestor progenitor species of cultivated peanut has also been of great interest. Several species have been suggested as putative AA and BB genome donors to allotetraploid A. hypogaea. Microsatellite or SSR (Simple Sequence Repeat) markers are co-dominant, multiallelic, and highly polymorphic genetic markers, appropriate for genetic diversity studies. Microsatellite markers may also, to some extent, support phylogenetic inferences. Here we report the use of a set of microsatellite markers, including newly developed ones, for phylogenetic inferences and the analysis of genetic variation of accessions of A. hypogea and its wild relatives. RESULTS: A total of 67 new microsatellite markers (mainly TTG motif) were developed for Arachis. Only three of these markers, however, were polymorphic in cultivated peanut. These three new markers plus five other markers characterized previously were evaluated for number of alleles per locus and gene diversity using 60 accessions of A. hypogaea. Genetic relationships among these 60 accessions and a sample of 36 wild accessions representative of section Arachis were estimated using allelic variation observed in a selected set of 12 SSR markers. Results showed that the Brazilian peanut germplasm collection has considerable levels of genetic diversity detected by SSR markers. Similarity groups for A. hypogaea accessions were established, which is a useful criteria for selecting parental plants for crop improvement. Microsatellite marker transferability was up to 76% for species of the section Arachis, but only 45% for species from the other eight Arachis sections tested. A new marker (Ah-041) presented a 100% transferability and could be used to classify the peanut accessions in AA and non-AA genome carriers. CONCLUSION: The level of polymorphism observed among accessions of A. hypogaea analyzed with newly developed microsatellite markers was low, corroborating the accumulated data which show that cultivated peanut presents a relatively reduced variation at the DNA level. A selected panel of SSR markers allowed the classification of A. hypogaea accessions into two major groups. The identification of similarity groups will be useful for the selection of parental plants to be used in breeding programs. Marker transferability is relatively high between accessions of section Arachis. The possibility of using microsatellite markers developed for one species in genetic evaluation of other species greatly reduces the cost of the analysis, since the development of microsatellite markers is still expensive and time consuming. The SSR markers developed in this study could be very useful for genetic analysis of wild species of Arachis, including comparative genome mapping, population genetic structure and phylogenetic inferences among species

Theory of pixel lensing towards M31 I: the density contribution and mass of MACHOs

POINT-AGAPE is an Anglo-French collaboration which is employing the Isaac Newton Telescope (INT) to conduct a pixel-lensing survey towards M31. In this paper we investigate what we can learn from pixel-lensing observables about the MACHO mass and fractional contribution in M31 and the Galaxy for the case of spherically-symmetric near-isothermal haloes. We employ detailed pixel-lensing simulations which include many of the factors which affect the observables. For a maximum MACHO halo we predict an event rate in V of up to 100 per season for M31 and 40 per season for the Galaxy. However, the Einstein radius crossing time is generally not measurable and the observed full-width half-maximum duration provides only a weak tracer of lens mass. Nonetheless, we find that the near-far asymmetry in the spatial distribution of M31 MACHOs provides significant information on their mass and density contribution. We present a likelihood estimator for measuring the fractional contribution and mass of both M31 and Galaxy MACHOs which permits an unbiased determination to be made of MACHO parameters, even from data-sets strongly contaminated by variable stars. If M31 does not have a significant population of MACHOs in the mass range 0.001-1 Solar masses strong limits will result from the first season of INT observations. Simulations based on currently favoured density and mass values indicate that, after three seasons, the M31 MACHO parameters should be constrained to within a factor four uncertainty in halo fraction and an order of magnitude uncertainty in mass (90% confidence). Interesting constraints on Galaxy MACHOs may also be possible. For a campaign lasting ten years, comparable to the lifetime of current LMC surveys, reliable estimates of MACHO parameters in both galaxies should be possible. (Abridged)Comment: 21 pages, 14 figures. Submitted to MNRA