Ex Vivo Evaluation of Insulin Nanoparticles Using Chitosan and Arabic Gum

Polymeric delivery systems based on nanoparticles have emerged as a promising approach for peroral insulin delivery. The aim of the present study was to investigate the release of insulin nanoparticulate systems and ex vivo studies. The nanoparticles were prepared by the ion gelation method. Particle size distribution, zeta potential, and polydispersity index of the nanoparticles were determined. It was found that the nanoparticles carried positive charges and showed a size distribution in the range of 170–200 nm. The electrostatic interactions between the positively charged group of chitosan and negatively charged groups of Arabic gum play an important role in the association efficiency of insulin in nanoparticles. In vitro insulin release studies showed an initial burst followed by a slow release of insulin. The mucoadhesion of the nanosystem was evaluated using excised rat jejunum. Ex vivo studies have shown a significant increase in absorption of insulin in the presence of chitosan nanoparticles in comparison with free insulin

Environmentally extended comparison table of large-versus small- and medium-scale fisheries : the case of the Peruvian anchoveta fleet

Literature on small-scale fisheries usually depicts them as preferable over large-scale-industrial fisheries regarding societal benefits (jobs, jobs per investment) and relative fuel efficiency (e. g., Thomson 1980). We propose an environmentally extended Thomson table for comparing the Peruvian anchoveta (Engraulis ringens) fleets of purse seiners, backed up by methodological information and augmented with life cycle assessment (LCA)-based environmental performance information, as a more comprehensive device for comparing fleets competing for the same resource pool. Findings from LCA and a previous study on the anchoveta steel fleet together allowed characterizing the whole Peruvian anchoveta fishery. These results, along with socioeconomic indicators, are used to build an environmentally extended Thomson table of the fleet's main segments: the steel industrial, the wooden industrial, and the wooden small-and medium-scale (SMS) fleets. In contrast with the world figure, the Peruvian SMS fleets show a fuel performance nearly two times worse than the industrial fleets, due to economies of scale of the latter (although the small-scale segment itself (<10 m(3)) performs similarly to the industrial steel fleet). Furthermore, the absolute number of jobs provided by the industrial fisheries is much larger in Peru than those provided by the SMS fisheries. This is due to the relatively larger development of the industrial fishery, but as in previous studies, the SMS fleets generate more employment per tonne landed than the industrial fleet, as well as more food fish and less discards at sea

"Oral ascorbic acid in combination with beta blockers in prevention of atrial fibrillation after Coronary Artery Bypass Graft "

Background: Adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass graft (CABG). This study was designed to evaluate the effect of ascorbic acid as an adjunct to beta-blockers in prevention of post-CABG atrial fibrillation Methods: Patients who were more than 50 years old and scheduled to undergo CABG were included if they were treated with beta-blockers at least 1 week before surgery. Patients with previous history of atrial fibrillation, AV block, heart rate &lt;50 /min, end-stage renal disease, severe pulmonary or liver disease and those who were taking digoxin or class I and III anti-arrhythmics or had pacemakers were not included. Ascorbic acid group were prescribed 2 gm of ascorbic acid, the night before the surgery, and 1 gm twice daily for 5 days after surgery. Beta blockers continued in both group after surgery. Telemetry monitoring was performed in ICU and Holter monitoring was performed for 4 days. Results: Fifty patients completed the study as ascorbic acid and 50 as control group. The population was 60.19 ± 7.14 years old and 67% were male. The incidence of postoperative atrial fibrillation was 4% in the ascorbic acid group and 26% in control group (odds ratio=0.119, 95% confidence interval: 0.025 to 0.558, P=0.002) Conclusion: Ascorbic acid is well-tolerated, relatively safe and seems effective. Therefore it can be prescribed as an adjunct to beta-blockers for prophylaxis of post-CABG atrial fibrillation

Permeation enhancer effect of chitosan and chitosan derivatives: comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells

In this study four quaternized derivatives of chitosan: trimethyl chitosan (TMC), dimethylethyl chitosan (DMEC), diethylmethyl chitosan (DEMC) and triethyl chitosan (TEC) with degree of substitution of approximately 50+/-5% were synthesized and their effect on the permeability of insulin across intestinal Caco-2 monolayers was studied and compared with chitosan both in free-soluble form and in nanoparticulate systems. Transepithelial electrical resistance (TEER) studies revealed that all four chitosan derivatives in free-soluble forms were able to decrease the TEER value in the following order TMC>DMEC>DEMC=TEC>chitosan, indicating their abilities to open the tight junctions. Recovery studies on the TEER showed that the effect of the polymers on Caco-2 cell monolayer is reversible and proves the viability of cells after incubation with all polymers. A similar rank order was also observed when measuring the zeta-potentials of the various polymers in solution form. Transport studies of insulin together with the soluble polymers across Caco-2 cell layers showed the following ranking: TMC>DMEC>DEMC>TEC>chitosan which is in agreement with the strength of the cationic charge of the polymer. In comparison to the free-soluble polymers, the nanoparticles prepared by ionic gelation of the chitosan and its quaternized derivatives had much lower effect on decreasing the TEER by opening of the tight junctions. This can be explained by the reduced available amount of positive charge at the surface of the nanoparticles. In accordance with these results, the insulin loaded nanoparticles showed much less permeation across the Caco-2 cell monolayer in comparison to the free-soluble polymers. Mass balance transport studies revealed that a substantial amount of the nanoparticles has been entrapped into the Caco-2 monolayer or attached to the cell surface. It can thus be stated that while free-soluble polymers can reversibly open the tight junctions and increase the permeation of insulin, the nanoparticles had basically only a low effect on the opening of the tight junction and the paracellular transport of insulin across the Caco-2 cell monolayer. These data convincingly show that nanoparticles consisting of chitosan and its quaternary ammonium derivatives loaded with insulin are less effective in facilitating paracellular transport across Caco-2 cell monolayers than the corresponding free polymers

Methylated N-(4-N,N-Dimethylaminobenzyl) Chitosan, a Novel Chitosan Derivative, Enhances Paracellular Permeability Across Intestinal Epithelial Cells (Caco-2)

The aim of this study was to investigate the effect of methylated N-(4-N,N-dimethylaminobenzyl) chitosan, TM-Bz-CS, on the paracellular permeability of Caco-2 cell monolayers and its toxicity towards the cell lines. The factors affecting epithelial permeability, e.g., degree of quaternization (DQ) and extent of dimethylaminobenzyl substitution (ES), were evaluated in intestinal cell monolayers of Caco-2 cells using the transepithelial electrical resistance and permeability of Caco-2 cell monolayers, with fluorescein isothiocyanate dextran 4,400 (FD-4) as a model compound for paracellular tight-junction transport. Cytotoxicity was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide viability assay. The results revealed that, at pH 7.4, TM-Bz-CS appeared to increase cell permeability in a concentration-dependent manner, and this effect was relatively reversible at lower doses of 0.05–0.5 mM. Higher DQ and the ES caused the permeability of FD-4 to be higher. The cytotoxicity of TM-Bz-CS depended on concentration, %DQ, and %ES. These studies demonstrated that this novel modified chitosan has potential as an absorption enhancer