The purpose of the present study was to develop intranasal delivery systems of sumatriptan using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation temperature below 34°C to ensure gelation at physiological temperature after intranasal administration. Gelation temperature was determined by physical appearance as well as by rheological measurement. The gelation temperatures of the formulations decreased by addition of increasing concentrations of Carbopol (ie, from 29°C for 18% PF127 to 23.9°C for 18% PF127, 0.5% Carbopol). The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of Carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation coefficient could be significantly increased by using in situ gelling formulation with Carbopol concentration 0.3% or greater. Finally, histopathological examination did not detect any damage during in vitro permeation studies. In conclusion, the PF127 gel formulation of sumatriptan with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging.

1. Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. 2. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. 3. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. 4. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. 5. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood.

Microemulsions are clear, transparent, thermodynamically stable dispersions of oil and water, stabilised by an interfacial film of surfactant frequently in combination with a co-surfactant. Recently, there has been a considerable interest for the microemulsion formulation, for the delivery of hydrophilic as well as lipophilic drug as drug carriers because of its improved drug solubilisation capacity, long shelf life, easy of preparation and improvement of bioavailability. In this present review, we discuss about the various advantages of microemulsion in pharmaceuticals, along with its composition variables, physicochemical characterisation etc. The potential use of microemulsion for therapeutic application is also discussed.

A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.

Endothelial cell (EC) movement is an initiating and rate-limiting event in the neogenesis and repair of blood vessels. Here, we explore the hypothesis that microviscosity of the plasma membrane (PM) is a key physiological regulator of cell movement. Aortic ECs treated with membrane-active agents, such as alpha-tocopherol, cholesterol and lysophospholipids, exhibited a biphasic dependency on membrane microviscosity, in which moderate increases enhanced EC migration, but increases beyond a threshold markedly inhibited migration. Surprisingly, angiogenic growth factors, that is, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), also increased membrane microviscosity, as measured in live cells by fluorescence recovery after photobleaching (FRAP). The localization of Rac to the PM was modified in cells treated with membrane-active agents or growth factors, suggesting a molecular mechanism for how membrane microviscosity influences cell movement. Our data show that angiogenic growth factors, as well as certain lipophilic molecules, regulate cell motility through alterations in membrane properties and the consequent relocalization of critical signalling molecules to membranes.

The main purpose of this work was to develop an oral microemulsion formulation for enhancing the bioavailability of acyclovir. A Labrafac-based microemulsion formulation with Labrasol as surfactant and Plurol Oleique as cosurfactant was developed for oral delivery of acyclovir. Phase behavior and solubilization capacity of the microemulsion system were characterized, and in vivo oral absorption of acyclovir from the microemulsion was investigated in rats. A single isotropic region, which was considered to be a bicontinuous microemulsion, was found in the pseudoternary phase diagrams developed at various Labrasol:Plurol Oleique:Labrafac ratios. With the increase of Labrasol concentration, the microemulsion region area and the amount of water and Labrafac solubilized into the microemulsion system increased; however, the increase of Plurol Oleique percentage produced opposite effects. The microemulsion system was also investigated in terms of other characteristics, such as interfacial tension, viscosity, pH, refractive index, diffusion, and bioavailability. Acyclovir, a poorly soluble drug, displayed high solubility in a microemulsion formulation using Labrafac (10%), Labrasol (32%), Plurol Oleique (8%), and water (50%). The in vitro intraduodenal diffusion and in vivo study revealed an increase of bioavailability (12.78 times) after oral administration of the microemulsion formulation as compared with the commercially available tablets.

The presence of brown adipose tissue (BAT) responsible for thermogenic energy dissipation has been revealed in adult humans and has high clinical importance. Due to limitations of current methods for BAT detection, analyzing the abundance and localization of BAT in the body has remained challenging. Here, we screen a combinatorial peptide library in mice and characterize a peptide (with the sequence CPATAERPC) that selectively binds to the vascular endothelium of BAT, but not of intraperitoneal white adipose tissue (WAT). We show that in addition to BAT, this peptide probe also recognizes the vasculature of BAT-like depots of subcutaneous WAT. Our results indicate that the CPATAERPC peptide localizes to BAT even in the absence of sympathetic nervous system stimulation. Finally, we demonstrate that this probe can be used to identify BAT depots in mice by whole body near-infrared (NIR) fluorescence imaging.