A main challenge in nanobiomedicine is the engineering of nanostructures or nanomaterials that can efficiently encapsulate drugs at high load, cross cell membranes, and controllably release their cargo at target sites. Although mesoporous silica nanoparticles (MSNs) are safe, versatile, and promising carrier materials for targeted drug delivery, their aggregation phenomena under physiological conditions (or salt-containing environments) and their nonspecific binding in protein-containing solutions (or serum) limit their applications in biological science and biomedicine. To address this challenge, we have developed a novel delivery system, termed a nanoshuttle, comprising a nanoscale PEGylated-phospholipid coating and 13-(chlorodimethylsilylmethyl)heptacosane-derivatized MSNs, in which therapeutic or imaging agents may be trapped and ligand-assisted targeted delivery may be achieved through surface functionalization of the phospholipids. As a proof of concept in this study, we selected fluorescein isothiocyanate and folate as the imaging tracer and targeted ligand, respectively. Relative to the bare MSNs, the lipid-capped MSNs exhibited superior suspensibility in phosphate-buffered saline and much lower nonspecific binding in vitro. Furthermore, enhanced specific cellular uptake by Hela cells occurred after administering the folate-sensitized phospholipid-capped MSNs. Our results suggest that these highly versatile multifunctional MSNs are promising vectors for nanomedicine applications.

Although the distal small intestine has less lumenal and apical proteolytic activities, it has high activities of some apical peptidases. Colonic proteolytic activities are substantial, but their nature is less understood. The small intestine has di- and tripeptide transporter, facilitating absorption, and P-glycoprotein, an efflux pump suggested to limit absorption of small peptides. Several peptide and nonpeptide drugs have higher absorption in the ileum; however, enhancement on their absorption by enhancers varies from site to site. Specific delivery systems can target drugs to the distal intestine utilizing distinct regional pHs and specific microbial enzymes, but the key is how to achieve a reliable release.

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The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging assay, reducing capacity and metal ion chelating capacity as well as total phenolic content of the extract were investigated. In addition, the inhibitory effects of ovatodiolide on mushroom tyrosinase, B16F10 intracellular tyrosinase and melanin content were determined spectrophotometrically. Our results revealed that the antioxidant capacities of A. indica methanol extract increased in a dose-dependent pattern. The purified ovatodiolide inhibited mushroom tyrosinase activity (IC50 = 0.253 mM), the compound also effectively suppressed intracellular tyrosinase activity (IC50 = 0.469 mM) and decreased the amount of melanin (IC50 = 0.435 mM) in a dose-dependent manner in B16F10 cells. Our results concluded that A. indica methanol extract displays antioxidant capacities and ovatodiolide purified from the extract inhibited melanogenesis in B16F10 cells. Hence, A. indica methanol extract and ovatodiolide could be applied as a type of dermatological whitening agent in skin care products.

IDE is the major enzyme which degrades insulin in enterocytes.

The objective of this study was to determine whether transepithelial transport of insulin can be improved by enzyme inhibitors and whether insulin concentration affects its ileal absorption. Ussing chambers and radioimmunoassay were used to study insulin transport across the rat ileum, and circular dichroic spectra were used to determine whether insulin aggregated at high concentrations. Inhibitors that inhibit insulin-degrading enzyme, including N-ethylmaleimide, 1,10-phenanthroline and p-chloromercuribenzoate, dramatically improved insulin transport across the ileum. At 100 nm, the ileal permeability of immunoreactive insulin was 10(-6) cm s-1 in the presence of inhibitors, and was negligible when inhibitors were not used. Ammonium chloride, a lysosomotropic agent that increases intralysosomal pH, and aprotinin, a proteasome inhibitor, did not increase transport of insulin to a detectable extent. Insulin permeability decreased as its concentration increased from 100 nm to 83.3 microM, and at 83.3 microM insulin aggregated. It is concluded that insulin transport is improved by enzyme inhibitors, but is impaired by insulin aggregation at high concentrations.

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Intestinal luminal degradation of neurotensin and acetylneurotensin-(8-13) within the gut of rats and rabbits was compared using brush-border membranes. Patterns of differential proteolysis of these two peptides within the intestine were similar within the same species and between the species. In both rats and rabbits, jejunal brush-border membranes had the highest proteolytic activities degrading neurotensin and acetylneurotensin-(8-13), and caecal or ileocaecal brush-border membranes had the lowest activities. In both species, patterns of site-dependent degradation of neurotensin and acetylneurotensin-(8-13) agreed with the distribution profiles of endopeptidase-24.11 and angiotensin-converting enzyme within the gut. The distal intestine of rats and rabbits has the lowest activities degrading these two compounds. The results demonstrate that distribution of peptidases within the gut will affect site-dependent degradation and absorption of peptide drugs.