PEG-PGA enveloped octaarginine-peptide nanocomplexes: An oral peptide delivery strategy.

The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a complex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer. The selected CPP was octaarginine (r8), chemically conjugated with cholesterol (Chol) or lauric acid (C12), whereas the protecting polymer was poly (glutamic acid)-poly (ethylene glycol) (PGA-PEG). This enveloping material was intended to preserve the stability of the nanocomplex in the intestinal medium and facilitate its diffusion across the intestinal mucus. The enveloped nanocomplexes (ENCPs) exhibited a number of key features, namely (i) a unimodal size distribution with a mean size of 200 nm and a neutral zeta potential, (ii) the capacity to associate insulin (~100% association efficiency) and protect it from degradation in simulated intestinal fluids, (iii) the ability to diffuse through intestinal mucus and, most importantly, (iv) the capacity to interact with the Caco-2 model epithelium, resulting in a massive insulin cell uptake (47.59 ±â€¯5.79%). This enhanced accumulation of insulin at the epithelial level was not translated into an enhanced insulin transport. In fact, only 2% of insulin was transported across the monolayer, and this was correlated with a moderate response of insulin following oral administration to healthy rats. Despite of this, the accumulation of the insulin-loaded nanocarriers in the intestinal mucosa could be verified in vivo upon their labeling with 99mTc. Overall, these data underline the capacity of the nanocarriers to overcome substantial barriers associated to the oral modality of administration and to facilitate the accumulation of the associated peptide at the intestinal level.

Improving green enrichment of virgin olive oil by oregano. Effects on antioxidants.

This work is about improvement of a maceration method in order to achieve a green process for the enrichment of virgin olive oil (VOO) with natural antioxidants, specifically from oregano leaves. This goal was accomplished after evaluating different mechanical methods, i.e. magnetic stirring, sonication, vertical stirring and sonication in combination with vertical stirring, for promoting the extraction of the antioxidants from oregano. The results obtained indicated that the best extraction procedure was vertical stirring at 1000 r.p.m. for 3 h. Therefore, these conditions were selected to enrich VOO with phenolic acids (mainly rosmarinic acid) and endogenous antioxidants (o-coumaric and vanillic acids), and further determine their stability at room temperature or under temperature stress (50°C) during 45 days. Quantitative analysis of rosmarinic, o-coumaric and vanillic acids was carried out by an off-line, solid phase extraction, capillary zone, electrophoresis method combined with diode-array detector (SPE-CE-DAD).