The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80-90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for >4h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptides.
Hepatic-related diseases, in particular hyperlipidemia and hypercholesterolemia, are a thorn on the side of the national health institutes around the globe. Indeed, liver lipid and cholesterol dysregulation could lead to atherosclerotic plaque formation and cardiovascular diseases. Currently, statin administration and monacolin K consumption are the main therapies proposed to counter this alarming connection, but relevant side effects are known. To overcome this issue, safe nutraceutical formulations and/or vegetal extracts, endowed with anticholesterolemic activity, could be instrumental in hypercholesterolemia prevention and treatment. In the present work, the anticholesterolemic efficacy of three vegetal extracts used in traditional medicine (artichoke, caigua, and fenugreek), their unique blend (ACFB), and the monacolin K-containing red yeast extract (RYR), was investigated with an in vitro approach based on hepatic cell line HepG2. The impact on cholesterol of the three extracts, their blend, and RYR were investigated by determining hepatocyte total and free cholesterol and bile acids biosynthesis. According to our results, the anticholesterolemic activity of the vegetal extracts was confirmed, and a novel choleretic activity of caigua extract was evidenced. ACFB showed to be safer than RYR while showing a similar effect on total and free cholesterol and bile acids synthesis compared to it. The anticholesterolemic activity of the blend was obtained with lower vegetal extract concentrations compared with the single vegetal extract, potentially indicating an additive effect between the extracts. In conclusion, the vegetal extracts and their blend, ACFB, are safe and are endowed with anticholesterolemic activity, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.
Silicon (Si) has numerous health properties. It is an element of the extracellular matrix; it is involved in collagen synthesis, bone mineralization, and immune system modulation; and it reduces metal accumulation in Alzheimer’s disease and the risk of atherosclerosis. Given its poor intestinal absorption, Si is ingested in the form of orthosilicic acid (OSA) to promote its bioavailability. The aim of this work was to compare different commercial dietary supplements containing stabilized OSA to ascertain their bioaccessibility, bioavailability, and safety in a model of human intestinal epithelium. Biocompatibility with the glycocalyx was also investigated. Supplements containing collagen, maltodextrins, and choline as OSA stabilizers were analyzed. Bioaccessibility was explored by means of an in vitro digestive process. Bioavailability was investigated using a Caco2 cell line alone, or co‐culturing with a HT29‐MTX cell line. The safety of the compounds tested (in terms of intestinal epithelium integrity) was judged on the grounds of MTS assay, transepithelial electrical resistance, and apparent permeability. The three formulations were also tested in a Caco2 cell model of intestinal glycocalyx Si retention. The choline‐formulated OSA formulation outperformed the maltodextrin‐stabilized supplement, with a Si bioavailability about 14 times higher (P < .05). The choline‐formulated OSA formulation increased cell permeability, with consequent intestinal epithelium disruption. The supplements’ absorption and bioavailability (and harmfulness) differed considerably, depending on the OSA stabilizer involved. Of the three formulations tested, the collagen‐formulated OSA represents the best Si dietary supplement.
The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue.
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