From Grape By-Products to Enriched Yogurt Containing Pomace Extract Loaded in Nanotechnological Nutriosomes Tailored for Promoting Gastro-Intestinal Wellness.

Grape pomace is the main by-product generated during the winemaking process; since it is still rich in bioactive molecules, especially phenolic compounds with high antioxidant power, its transformation in beneficial and health-promoting foods is an innovative challenge to extend the grape life cycle. Hence, in this work, the phytochemicals still contained in the grape pomace were recovered by an enhanced ultrasound assisted extraction. The extract was incorporated in liposomes prepared with soy lecithin and in nutriosomes obtained combining soy lecithin and Nutriose FM06®, which were further enriched with gelatin (gelatin-liposomes and gelatin-nutriosomes) to increase the samples' stability in modulated pH values, as they were designed for yogurt fortification. The vesicles were sized ~100 nm, homogeneously dispersed (polydispersity index < 0.2) and maintained their characteristics when dispersed in fluids at different pH values (6.75, 1.20 and 7.00), simulating salivary, gastric and intestinal environments. The extract loaded vesicles were biocompatible and effectively protected Caco-2 cells against oxidative stress caused by hydrogen peroxide, to a better extent than the free extract in dispersion. The structural integrity of gelatin-nutriosomes, after dilution with milk whey was confirmed, and the addition of vesicles to the yogurt did not modify its appearance. The results pointed out the promising suitability of vesicles loading the phytocomplex obtained from the grape by-product to enrich the yogurt, offering a new and easy strategy for healthy and nutritional food development.

Design and in vitro effectiveness evaluation of Echium amoenum extract loaded in bioadhesive phospholipid vesicles tailored for mucosal delivery.

The Echium amoenum Fisch. and C.A. Mey. (E. amoenum) is an herb native from Iranian shrub, and its blue-violet flowers are traditionally used as medical plants. In the present study, an antioxidant phytocomplex was extracted from the flowers of E. amoenum by ultrasounds-assisted hydroalcoholic maceration. The main components, contained in the extract, have been detected using HPLC-DAD, and rosmarinic acid was found to be the most abundant. The antioxidant power of the extract along with the phenolic content were measured using colorimetric assays. The extract was loaded in liposomes, which were enriched adding different bioadhesive polymers (i.e., mucin, xanthan gum and carboxymethyl cellulose sodium salt) individually or in combination. The main physico-chemical properties (i.e. size, size distribution, surface charge) of the prepared vesicles were measured as well as their stability on storage. The viscosity of dispersion and the ability of vesicles to interact with mucus were evaluated measuring their stability in a mucin dispersion and mobility in a mucin film. The biocompatibility and the ability of the formulations to protect keratinocytes from damages caused by hydrogen peroxide and to promote the cell migration were measured in vitro.

Nanotechnology for Natural Medicine: Formulation of Neem Oil Loaded Phospholipid Vesicles Modified with Argan Oil as a Strategy to Protect the Skin from Oxidative Stress and Promote Wound Healing.

Neem oil, a plant-derived product rich in bioactives, has been incorporated in liposomes and hyalurosomes modified by adding argan oil and so called argan-liposomes and argan-hyalurosomes. Argan oil has also been added to the vesicles because of its regenerative and protective effects on skin. In the light of this, vesicles were specifically tailored to protect the skin from oxidative stress and treat lesions. Argan-liposomes were the smallest vesicles (~113 nm); the addition of sodium hyaluronate led to an increase in vesicle size (~143 nm) but it significantly improved vesicle stability during storage. In vitro studies confirmed the free radical scavenging activity of formulations, irrespective of their composition. Moreover, rheological investigation confirmed the higher viscosity of argan-hyalurosomes, which avoid formulation leakage after application. In vitro studies performed by using the most representative cells of the skin (i.e., keratinocytes and fibroblasts) underlined the ability of vesicles, especially argan-liposomes and argan-hyalurosomes, to counteract oxidative stress induced in these cells by using hydrogen peroxide and to improve the proliferation and migration of cells ensuring the more rapid and even complete closure of the wound (scratch assay).

Trimethyl Chitosan Hydrogel Nanoparticles for Progesterone Delivery in Neurodegenerative Disorders.

Progesterone is a sex hormone which shows neuroprotective effects in different neurodegenerative disorders, including Parkinson's disease, stroke, and Alzheimer's disease. However, the pharmacokinetic limitations associated with the peripheral administration of this molecule highlight the need for more efficient delivery approaches to increase brain progesterone levels. Since the nose-to-brain administration of mucoadhesive hydrogel nanoparticles is a non-invasive and convenient strategy for the delivery of therapeutics to the central nervous system, in this work, progesterone-loaded hydrogel nanoparticle formulations have been prepared, characterized, and tested in vivo. Nanoparticles, loaded with different progesterone concentrations, have been obtained by polyelectrolyte complex formation between trimethyl chitosan and sodium alginate, followed by ionotropic gelation with sodium tripolyphosphate as a cross-linking agent. All formulations showed a mean diameter ranging from 200 nm to 236 nm, a polydispersity index smaller than 0.23, and a high progesterone encapsulation efficiency (83-95%). The zeta potential values were all positive and greater than 28 mV, thus ensuring nanoparticles stability against aggregation phenomena as well as interaction with negative sialic residues of the nasal mucosa. Finally, in vivo studies on Sprague-Dawley male rats demonstrated a 5-fold increase in brain progesterone concentrations compared to basal progesterone level after 30 min of hydrogel nanoparticle inhalation.

Cavitation effect on chitosan nanoparticle size: a possible approach to protect drugs from ultrasonic stress.

The objective of this study was to verify the influence of different modes of ultrasonic radiation on both the mean diameter and the polydispersity index (PI) of chitosan (CH) nanoparticles, which were prepared by means of the ionotropic gelation method. The variations in duration, intensity and mode of cycle of ultrasonic radiation allowed us to highlight several optimal treatments in order to obtain a potential carrier for site-specific drug delivery. Despite the high utility, ultrasound may be a risk factor for sensitive drug-loaded nanoparticles; in order to protect the drug from thermal or mechanical stress, the effects of ultrasonic radiation only on the CH dispersion (instead of the chitosan/tripolyphosphate (TPP) mixture) were studied, without damaging the drug added to the TPP solution. The increase of the wave amplitude, mode of cycle and time of sonication decreased the particle mean diameter; moreover, the mode of cycle showed a greater effect than the other parameters on the PI of the nanoparticle system. Both the mean diameter and the PI of CH nanoparticles increased with increasing CH concentration. The application of ultrasound only on the CH dispersion showed interesting results, particularly in regard to formulations prepared from low and medium molecular weight chitosan.