The Next Generation Non-competitive Active Polyester Nanosystems for Transferrin Receptor-mediated Peroral Transport Utilizing Gambogic Acid as a Ligand

The current methods for targeted drug delivery utilize ligands that must out-compete endogenous ligands in order to bind to the active site facilitating the transport. To address this limitation, we present a non-competitive active transport strategy to overcome intestinal barriers in the form of tunable nanosystems (NS) for transferrin receptor (TfR) utilizing gambogic acid (GA), a xanthanoid, as its ligand. The NS made using GA conjugated poly(lactide-co-glycolide) (PLGA) have shown non-competitive affinity to TfR evaluated in cell/cell-free systems. The fluorescent PLGA-GA NS exhibited significant intestinal transport and altered distribution profile compared to PLGA NS in vivo. The PLGA-GA NS loaded with cyclosporine A (CsA), a model peptide, upon peroral dosing to rodents led to maximum plasma concentration of CsA at 6 h as opposed to 24 h with PLGA-NS with at least 2-fold higher levels in brain at 72 h. The proposed approach offers new prospects for peroral drug delivery and beyond

FORMULATION AND EVALUATION OF GEL LOADED WITH MICROSPHERES OF APREMILAST FOR TRANSDERMAL DELIVERY SYSTEM

Objective: The main objective of the present research work was to formulate and evaluate gel loaded with microspheres of apremilast to increase bioavailability and to reduce the dosing frequency and to improve patient compliance. Methods: Gel loaded with microspheres of apremilast was prepared by solvent evaporation method by taking different ratios of polymers. Ethyl cellulose as a polymer, dichloromethane solvent is used as drug solubility, polyvinyl alcohol as a surfactant, and sodium alginate is used as gelling agent. Prepared gel loaded with microspheres was evaluated for drug interactions by Fourier transform infrared (FTIR), differential scanning calorimetry studies, and surface morphology by scanning electron microscopy (SEM), to select effective one among all formulations. The prepared formulations (F1–F6) were evaluated for pre-formulation studies, spreadability, viscosity, pH measurement, gel strength, homogeneity, drug content, in vitro diffusion studies, drug kinetics, and finally for stability studies. Results: Differential scanning calorimeter studies confirmed that there is no drug interaction between drug and excipients. FTIR spectroscopy studies confirmed that there is compatibility between drug and excipients. Regular and spherical shape particles with smooth surface were observed in the SEM photographs. The optimized gel loaded with microspheres of F4 formulation (drug: polymer in 1:4 ratio) is more effective compared to all formulations. The prepared gel showed acceptable physical properties such as spreadability (5.86±0.54 g.cm/s), viscosity (568 cps), pH (6.33±0.55), gel strength (38 s) and drug content (90.00±0.71%). In vitro diffusion studies have shown 80.1±1.92% drug release in 10 h. Drug kinetics follows zero order kinetics and n value was found to be 0.721. Stability studies were done for 3 months. Conclusion: All the results show that the gel loaded with microspheres of apremilast can be effectively used for the treatment of psoriasis and psoriatic arthritis

2-(2,6-Dimethoxy­phen­yl)-5-hydr­oxy-7-meth­oxy-4H-1-benzopyran-4-one

In the title compound, C18H16O6, the dimethoxy­phenyl ring is rotated by 61.8 (1)° from the plane of the benzopyran system. The mol­ecule is stabilized by an intra­molecular O—H⋯O hydrogen bond

Recognition schemes for protein-nucleic acid interactions

The molecular forces involved in protein-nucleic acid interaction are electrostatic, stacking and hydrogen-bonding. These interactions have a certain amount of specificity due to the directional nature of such interactions and the spatial contributions of the steric effects of different substituent groups. Quantum chemical calculations on these interactions have been reported which clearly bring out such features. While the binding energies for electrostatic interactions are an order of magnitude higher, the differences in interaction energies for structures stabilised by hydrogen-bonding and stacking are relatively small. Thus, the molecular interactions alone cannot explain the highly specific nature of binding observed in certain segments of proteins and nucleic acids. It is therefore logical to assume that the sequence dependent three dimensional structures of these molecules help to place the functional groups in the correct geometry for a favourable interaction between the two molecules. We have carried out 2D-FT nuclear magnetic resonance studies on the oligonucleotide d-GGATCCGGATCC. This oligonucleotide sequence has two binding sites for the restriction enzyme Bam H1. Our studies indicate that the conformation of this DNA fragment is predominantly B-type except near the binding sites where the ribose ring prefers a3E conformation. This interesting finding raises the general question about the presence of specificity in the inherent backbone structures of proteins and nucleic acids as opposed to specific intermolecular interactions which may induce conformational changes to facilitate such binding

Critical currents in vicinal YBa2_2Cu3_3O7−δ_{7-\delta} films

Most measurements of critical current densities in YBa$_2$Cu$_3$O$_{7-\delta}$ thin films to date have been performed on films where the \textit{c}-axis is grown normal to the film surface. With such films, the analysis of the dependence of $j_c$ on the magnetic field angle is complex. The effects of extrinsic contributions to the angular field dependence of $j_c$, such as the measurement geometry and disposition of pinning centres, are convoluted with those intrinsically due to the anisotropy of the material. As a consequence of this, it is difficult to distinguish between proposed FLL structure models on the basis of angular critical current density measurements on \textit{c}-axis films. Films grown on mis-cut (vicinal) substrates have a reduced measurement symmetry and thus provide a greater insight into the critical current anisotropy. In this paper previous descriptions of the magnetic field angle dependence of $j_c$ in YBa$_2$Cu$_3$O$_{7-\delta}$ are reviewed. Measurements on YBa$_2$Cu$_3$O$_{7-\delta}$ thin films grown on a range of vicinal substrates are presented and the results interpreted in terms of the structure and dimensionality of the FLL in YBa$_2$Cu$_3$O$_{7-\delta}$. There is strong evidence for a transition in the structure of the flux line lattice depending on magnetic field magnitude, orientation and temperature. As a consequence, a simple scaling law can not, by itself, describe the observed critical current anisotropy in YBa$_2$Cu$_3$O$_{7-\delta}$. The experimentally obtained $j_c(\theta)$ behaviour of YBCO is successfully described in terms of a kinked vortex structure for fields applied near parallel to the \textit{a-b} planes.Comment: 10 pages, 12 figures, Submitted to PR

Assessing unrealized yield potential of maize producing districts in India

The projected demand of maize production in India in 2050 is 4–5 times of current production. With the scope for area expansion being limited, there is need for enhancement of yield. This calls for identifying areas where huge unrealized yield potential exists. With a view to address the issue, the present study delineates homogeneous agro-climatic zones for maize production system in India taking district as a unit and using the factors production, viz. climate, soil, season and irrigated area under the crop. There are 146 districts in India that grow maize as a major crop. They were divided into 26 zones using multivariate cluster analysis. Study of variation in yield between districts within a zone vis-à-vis crop management practices adopted in those districts was found useful in targeting the yield gaps. These findings can have direct relevance to the maize farmers and district level administrators

Native Environment Modulates Leaf Size and Response to Simulated Foliar Shade across Wild Tomato Species

The laminae of leaves optimize photosynthetic rates by serving as a platform for both light capture and gas exchange, while minimizing water losses associated with thermoregulation and transpiration. Many have speculated that plants maximize photosynthetic output and minimize associated costs through leaf size, complexity, and shape, but a unifying theory linking the plethora of observed leaf forms with the environment remains elusive. Additionally, the leaf itself is a plastic structure, responsive to its surroundings, further complicating the relationship. Despite extensive knowledge of the genetic mechanisms underlying angiosperm leaf development, little is known about how phenotypic plasticity and selective pressures converge to create the diversity of leaf shapes and sizes across lineages. Here, we use wild tomato accessions, collected from locales with diverse levels of foliar shade, temperature, and precipitation, as a model to assay the extent of shade avoidance in leaf traits and the degree to which these leaf traits correlate with environmental factors. We find that leaf size is correlated with measures of foliar shade across the wild tomato species sampled and that leaf size and serration correlate in a species-dependent fashion with temperature and precipitation. We use far-red induced changes in leaf length as a proxy measure of the shade avoidance response, and find that shade avoidance in leaves negatively correlates with the level of foliar shade recorded at the point of origin of an accession. The direction and magnitude of these correlations varies across the leaf series, suggesting that heterochronic and/or ontogenic programs are a mechanism by which selective pressures can alter leaf size and form. This study highlights the value of wild tomato accessions for studies of both morphological and light-regulated development of compound leaves, and promises to be useful in the future identification of genes regulating potentially adaptive plastic leaf traits

Swift Heavy Ion Induced Modification Studies of C60 Thin Films

Modification induced by 110 MeV Ni ion irradiated thin film samples of C60 on Si and quartz substrates were studied at various fluences. The pristine and irradiated samples were investigated using Raman spectroscopy, electrical conductivity and optical absorption spectroscopy. The Raman data and band gap measurements indicate that swift ions at low fluences result in formations that involve multiple molecular units like dimer or polymer. High fluence irradiation resulted in sub-molecular formations and amorphous semiconducting carbon, indicating overall damage of the fullerene molecules. These sub-molecular units have been identified with nanocrystalline diamond and nanocrystalline graphite like formations.Comment: 7 pages, 29 references and 9 figures submitted to J. Appl. Phy

Parameter estimation in spatially extended systems: The Karhunen-Loeve and Galerkin multiple shooting approach

Parameter estimation for spatiotemporal dynamics for coupled map lattices and continuous time domain systems is shown using a combination of multiple shooting, Karhunen-Loeve decomposition and Galerkin's projection methodologies. The resulting advantages in estimating parameters have been studied and discussed for chaotic and turbulent dynamics using small amounts of data from subsystems, availability of only scalar and noisy time series data, effects of space-time parameter variations, and in the presence of multiple time-scales.Comment: 11 pages, 5 figures, 4 Tables Corresponding Author - V. Ravi Kumar, e-mail address: [email protected]