Comparison of virus-capsid mimicking biologic-shell based versus polymeric-shell nanoparticles for enhanced oral insulin delivery

Virus-capsid mimicking mucus-permeable nanoparticles are promising oral insulin carriers which surmount intestinal mucus barrier.However,the impact of different viruscapsid mimicking structure remains unexplored.In this study,utilizing biotin grafted chitosan as the main skeleton,virus-mimicking nanoparticles endowed with biologicshell(streptavidin coverage)and polymeric-shell(hyaluronic acid/alginate coating)were designed with insulin as a model drug by self-assembly processes.It was demonstrated that biologic-shell mimicking nanoparticles exhibited a higher intestinal trans-mucus(>80%,10 min)and transmucosal penetration efficiency(1.6–2.2-fold improvement)than polymeric-shell counterparts.Uptake mechanism studies revealed caveolae-mediated endocytosis was responsible for the absorption of biologic-shell mimicking nanoparticles whereas polymeric-shell mimicking nanoparticles were characterized by clathrin-mediated pathway with anticipated lysosomal insulin digestion.Further,in vivo hypoglycemic study indicated that the improved effect of regulating blood sugar levels was virus-capsid structure dependent out of which biologic-shell mimicking nanoparticles presented the best performance(5.1%).Although the findings of this study are encouraging,much more work is required to meet the standards of clinical translation.Taken together,we highlight the external structural dependence of virus-capsid mimicking nanoparticles on the mucopenetrating and uptake mechanism of enterocytes that in turn affecting their in vivo absorption,which should be pondered when engineering virus-mimicking nanoparticles for oral insulin delivery.

Nano-enabled agglomerates and compact:Design aspects of challenges

Nanoscale medicine confers passive and active targeting potential.The development of nanomedicine is however met with processing,handling and administration hurdles.Excessive solid nanoparticle aggregation and caking result in lowproduct yield,poor particle flowability and inefficient drug administration.These are overcome by converting the nanoparticles into a microscale dosage form via agglomeration or compaction techniques.Agglomeration and compaction nonetheless predispose the nanoparticles to risks of losing their nanogeometry,surface composition or chemistry being altered and negating biological performance.This study reviews risk factors faced during agglomeration and compaction that could result in these changes to nanoparticles.The potential risk factors pertain to materials choice in nanoparticle and microscale dosage form development,and their interplay effects with process temperature,physical forces and environmental stresses.To render the physicochemical and biological behaviour of the nanoparticles unaffected by agglomeration or compaction,modes to modulate the interplay effects of material and formulation with processing and environment variables are discussed.

A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity

This review focuses on the efficacy and safety of effective herbal medicines in the management of obesity in humans and animals. PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to December 30, 2008. The search terms were ＂obesity＂ and （＇herbal medicine＂ or ＂plant＂, ＂plant medicinal＂ or ＂medicine traditional＂） without narrowing or limiting search elements. All of the human and animal studies on the effects of herbs with the key outcome of change in anthropometric measures such as body weight and waist-hip circumference, body fat, amount of food intake, and appetite were included. In vitro studies, reviews, and letters to editors were excluded. Of the publications identified in the initial database, 915 results were identified and reviewed, and a total of 77 studies were included （19 human and 58 animal studies）. Studies with Cissus quadrangularis （CQ）, Sambucus nigra, Asparagus officinalis, Garcinia atroviridis, ephedra and caffeine, Slimax （extract of several plants including Zingiber officinale and Bofutsushosan） showed a significant decrease in body weight. In 41 animal studies, significant weight loss or inhibition of weight gain was found. No significant adverse effects or mortality were observed except in studies with supplements containing ephedra, caffeine and Bofutsushosan. In conclusion, compounds containing ephedra, CQr ginseng, bitter melon, and zingiber were found to be effective in the management of obesity. Attention to these natural compounds would open a new approach for novel therapeutic and more effective agents.

Islet transplantation and antioxidant management: A comprehensive review

Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008. All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insuffi cient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefi ts of antioxidants in islet isolation procedures cannot be ignored.

Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation.Blending nanoparticles with lactose microparticles(~5 μm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000(PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products(fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.

Amide Ionic Liquids(AILs)/L-Proline Synergistic Catalyzed Asymmetric Mannich Reactions

Amide ionic liquids （MLs）/L-proline synergistic catalyzed Mannich reactions of isovaleraldehyde, methyl ketones, and aromatic amines were carried out in moderate to high yields （ up to 96% ） and high stereo selectivities （ 〉99% e. e. ）. The products were easily isolated by extraction; and the catalyst system was readily recycled at least thrice without significant loss of efficiency. The scope of the substrates was studied and the interpretation of the manifest improvement of the reaction rates and enantio-selectivity of the novel catalyst system was speculated.

Distribution and variability of n-alkanes in waxes of conifers

Epicuticular waxes have vital roles in the growth and development of plants and in defense. Conifers have a considerable amount of waxes on their cones and leaves.Here we characterized the n-alkane composition of Iranian conifers, including Juniperus oblonga, J. foetidissima, J.sabina, J. communis subsp. hemisphaerica, J. excelsa,Cupressus sempervirens, Platycladus orientalis from Cupressaceae and Taxus baccata from Taxaceae for the first time using GC-FID analyses. In the waxes, 25 n-alkane homologs with chain lengths ranging from C7 to C32 were identified. Short-chain n-alkanes were dominant in almost all samples with some exceptions. Complementary studies to elucidate complete wax constituents of Iranian conifers and n-alkane distribution pattern as a function of geographical and bioclimatic variables are recommended.

Facile Aldol Reaction Between Unmodified Aldehydes and Ketones in Bronsted Acid Ionic Liquids

A series of condensation reactions of unmodified ketones and aromatic aldehydes to prepare α,β-unsaturated carbonyl compounds by means of Aldol reactions in Bronsted acid ionic liquids（BAILs）was explored.1-Butyl-3-methylimidazolium hydrogen sulphate（BMImHSO4）acting as an effective media and catalyst in aldol reactions was compared with other BAILs,with the advantages of high conversion and selectivity.The product was easily isolated and the left ionic liquid can be readily recovered and reused at least 3 times with almost the same efficiency.The scope and limitation of the present method were explored and the possible catalytic mechanism was speculated.

Microwave technology enabled transdermal nanocarrier and drug delivery

Transdermal drug delivery is impeded by the natural barrier of epidermis known as stratum corneum.This limits the route to transport of drugs with a log octanol–water partition coefficient of 1 to 3,molecular weight of less than 500 Da and melting point of less than 200°C.Nanotechnology has received a widespread investigation as the nanocarriers are able to fluidize the stratum corneum as a function of size,shape,surface charges,and hydrophilicity–hydrophobicity balance,while delivering drugs across the skin barrier.

Association between Plasma Myeloperoxidase and Free 3-Nitrotyrosine Levels in Patients with Coronary Artery Disease

Objective: Myeloperoxidase (MPO) is an inflammatory enzyme that is mainly released by activated neutrophils and monocytes. 3-nitrotyrosine (NT) is a stable inflammatory end product of MPO that is produced through nitrosylation of free and protein-bound tyrosines. Determination of the exact levels of free NT is technically a challenging matter. Also, there is limited information about the relationship between MPO and free NT levels and elevation of them in the plasma of patients with coronary artery disease (CAD). Therefore, we sought to determine the exact level of plasma free NT with a simple and exquisite technique in CAD patients. Methods: This study included 50 stable angina, 50 unstable angina patients, and 50 control subjects. Plasma MPO concentration was measured with an immunoassay method. Plasma free NT level was determined by a modified HPLC-fluorescence method. Lipid profile, high sensitivity C-reactive protein (hsCRP) and other clinical risk factors of patients were also assigned. Results: Plasma level of free NT was efficiently measured by the HPLC-fluorescence method. Plasma levels of MPO and NT were significantly higher in patients with stable and unstable CAD than in control subjects (P < 0.001). There was a significant correlation between the two substances in CAD patients (P < 0.001). Conclusions: We determined plasma free NT levels with a sensitive HPLC-fluorescence method with some modifications in a clinical scale. Plasma levels of MPO and NT were profoundly elevated in CAD patients. The significant relationships of the two substances and elevation of them may have useful clinical implication in patients with stable and unstable CAD.

Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs

Several different pharmacological effects have been described for Nigella sativa(Siah-Daneh) ,including an anti-inflammatory effect.In the present study,the effect of the extract of N.sativa on lung pathology and blood interleukin-4(IL-4) and interferon-γ(IFN-γ) of sensitized guinea pigs was examined.Three groups(n=8 for each group) of guinea pigs sensitized to ovalbumin(OA) were given drinking water alone,and drinking water containing low and high concentrations of the plant extract,respectively.The animals of the control group(n=8) were treated with saline instead of OA and were given drinking water.The pathological changes of the lung,including infiltration of eosinophils and lymphocytes,local epithelial necrosis,the presence of oedema,thickening of the basement membrane,smooth muscle layer hypertrophy,mucosal secretion,and the presence of mucosal plug,and blood IL-4 and IFN-γof sensi-tized guinea pigs were evaluated.The lungs of the sensitized group showed significant pathological changes(P<0.001) .Blood IL-4 and IFN-γwere increased in sensitized animals compared to the controls(P<0.01 and P<0.001,respectively) .Treatment of sensitized animals with the extract led to a significant decrease in pathological changes of the lung(P<0.01 to P<0.001) ,except for the oedema in the sensitized group treated with low concentration of the extract,but an increased IFN-γ.These results confirm a preventive effect of N.sativa extract on lung inflammation of sensitized guinea pigs.