Exhausted Grape Seed Residues as a Valuable Source of Antioxidant Molecules for the Formulation of Biocompatible Cosmetic Scrubs.

Grape seed of Obeidi, a white Lebanese autochthonous variety, was previously tested in different studies as a valuable source of bioactive molecules such as polyphenols, oils, and proteins by means of extraction procedures for the development of cosmetic and therapeutic products. However, an un-valorized, exhausted grape seed residue remains as "secondary waste" after the extraction processes. In this study, the exhausted seeds have been further exploited to produce cosmetic scrubs capable of releasing antioxidant molecules during the exfoliation process, in accordance with the principles of the circular economy and going toward a zero-waste process. The deep characterization of the exhausted seeds confirmed the presence of antioxidant phenolic molecules including gallic acid, catechins and protocatechuic acid (0.13, 0.126, and 0.089 mg/g of dry matter DM), and a high phenolic content (11.85 mg gallic acid equivalents (GAE)/g of dry matter (DM)). Moreover, these residues were shown to possess a sandy texture (Hausner ratio (HR): 1.154, Carr index (CI): 0.133, and angle of repose: 31.62 (°) degrees), similar to commercial natural exfoliants. In this respect, exhausted Obeidi grape seed residues were incorporated at increasing concentrations (0.5, 1, 1.5, and 2% w/w) in a cosmetic scrub, and stored for 5 weeks at 4, 25, and 50 °C for stability testing. All tested scrub formulations exhibited good spreadability with a spread diameter of 3.6-4.7 cm and excellent physical stability, as no phase separation or color change were observed after four cycles of heat shock at 4 and 50 °C. Finally, an in vivo skin irritation test showed that the scrub enriched with 1.5% of exhausted Obeidi grape seed residues was the most promising formulation, as it possessed a high amount of phenolic molecules (0.042 ± 0.001 mg GAE/mL of scrub) and good stability and could be safely applied to the skin with no irritation phenomena. Overall results underlined that exhausted grape seed residues can be transformed into promising systems for both physical and chemical exfoliation, thus confirming the importance of the effective exploitation of agro-industrial by-products for the development of high value cosmeceutics towards a more sustainable and zero-waste approach.

Formulation and Testing of Antioxidant and Protective Effect of Hyalurosomes Loading Extract Rich in Rosmarinic Acid Biotechnologically Produced from Lavandula angustifolia Miller.

Culture of plant cells or tissues is a scalable, sustainable, and environmentally friendly approach to obtain extracts and secondary metabolites of uniform quality that can be continuously supplied in controlled conditions, independent of geographical and seasonal variations, environmental factors, and negative biological influences. In addition, tissues and cells can be extracted/obtained from the by-products of other industrial cultivations such as that of Lavandula angustifolia Miller (L. angustifolia), which is largely cultivated for the collection of flowers. Given that, an extract rich in rosmarinic acid was biotechnologically produced starting from cell suspension of L. angustifolia, which was then loaded in hyalurosomes, special phospholipid vesicles enriched with sodium hyaluronate, which in turn are capable of both immobilizing and stabilizing the system. These vesicles have demonstrated to be good candidates for skin delivery as their high viscosity favors their residence at the application site, thus promoting their interaction with the skin components. The main physico-chemical and technological characteristics of vesicles (i.e., mean diameter, polydispersity index, zeta potential and entrapment efficiency of extract in vesicles) were measured along with their biological properties in vitro: biocompatibility against fibroblasts and ability to protect the cells from oxidative stress induced by hydrogen peroxide. Overall, preliminary results disclosed the promising properties of obtained formulations to be used for the treatment of skin diseases associated with oxidative stress and inflammation.

Jabuticaba (Myrciaria jaboticaba) Peel as a Sustainable Source of Anthocyanins and Ellagitannins Delivered by Phospholipid Vesicles for Alleviating Oxidative Stress in Human Keratinocytes.

The Brazilian berry scientifically known as jabuticaba is a fruit covered by a dark purple peel that is still rich in bioactives, especially polyphenols. Considering that, this work was aimed at obtaining an extract from the peel of jabuticaba fruits, identifying its main components, loading it in phospholipid vesicles specifically tailored for skin delivery and evaluating their biological efficacy. The extract was obtained by pressurized hot water extraction (PHWE), which is considered an easy and low dissipative method, and it was rich in polyphenolic compounds, especially flavonoids (ortho-diphenols and condensed tannins), anthocyanins (cyanidin 3-O-glucoside and delphinidin 3-O-glucoside) and gallic acid, which were responsible for the high antioxidant activity detected using different colorimetric methods (DPPH, FRAP, CUPRAC and metal chelation). To improve the stability and extract effectiveness, it was incorporated into ultradeformable phospholipid vesicles (transfersomes) that were modified by adding two different polymers (hydroxyethyl cellulose and sodium hyaluronate), thus obtaining HEcellulose-transfersomes and hyaluronan-transfersomes. Transfersomes without polymers were the smallest, as the addition of the polymer led to the formation of larger vesicles that were more stable in storage. The incorporation of the extract in the vesicles promoted their beneficial activities as they were capable, to a greater extent than the solution used as reference, of counteracting the toxic effect of hydrogen peroxide and even of speeding up the healing of a wound performed in a cell monolayer, especially when vesicles were enriched with polymers. Given that, polymer enriched vesicles may represent a good strategy to produce cosmetical and cosmeceutical products with beneficial properties for skin.

Design of a Nasal Spray Based on Cardiospermum halicacabum Extract Loaded in Phospholipid Vesicles Enriched with Gelatin or Chondroitin Sulfate.

The extract of Cardiospermum halicacabum L. (C. halicacabum) obtained from flower, leaf and vine was loaded into modified phospholipid vesicles aiming at obtaining sprayable, biocompatible and effective nasal spray formulations for the treatment of nasopharyngeal diseases. Penetration enhancer-containing vesicles (PEVs) and hyalurosomes were formulated, and stabilized by adding a commercial gelatin from fish (20 mg/mL) or chondroitin sulfate from catshark cartilages (Scyliorhinus canicula, 20 mg/mL). Cryo-TEM images confirmed the formation of spherical vesicles, while photon correlation spectroscopy analysis disclosed the formation of small and negatively-charged vesicles. PEVs were the smaller vesicles (~100 nm) along with gelatin-hyalurosomes (~120 nm), while chondroitin-PEVs and chondroitin-hyalurosomes were larger (~160 nm). Dispersions prepared with chondroitin sulfate were more homogeneous, as the polydispersity index was ~0.15. The in vitro analysis of the droplet size distribution, average velocity module and spray cone angle suggested a good spray-ability and deposition of formulations in the nasal cavity, as the mean diameter of the droplets was in the range recommended by the Food and Drug Administration for nasal targets. The spray plume analysis confirmed the ability of PEVs, gelatin-PEVs, hyalurosomes and gelatin-hyalurosomes to be atomized in fine droplets homogenously distributed in a full cone plume, with an angle ranging from 25 to 30°. Moreover, vesicles were highly biocompatible and capable of protecting the epithelial cells against oxidative damage, thus preventing the inflammatory state.

A liposome-based formulation containing equol, dihomo-γ-linolenic acid and propionyl-l-carnitine to prevent and treat hair loss: A prospective investigation.

Hair loss is a common aesthetic disorder that can be triggered by genetic, inflammatory, hormonal, and environmental factors acting on hair follicles and their life cycle. There are several types of hair loss that differ in causes, symptoms, and spatial and temporal progression. Androgenic alopecia, a common form of hair loss, is the consequence of a decreased microcirculation of the scalp as well as the toxic action of elevated dihydrotestosterone levels on the hair bulbs. In the present study, the lotions TRINOV Lozione Anticaduta Uomo and TRINOV Lozione Anticaduta Donna, containing dihomo-γ-linolenic acid (DGLA), S-equol, and propionyl-l-carnitine, were tested on 30 men and 30 women (mean age of men was 46.6 ± 6.4 years; mean age of women was 49.5 ± 9.0) with signs of androgenic alopecia, respectively. DGLA is a precursor of the prostaglandin PGE1, which acts by improving microcirculation; S-equol inhibits 5α-reductases, thus preventing the transformation of testosterone into dihydrotestosterone; and propionyl-l-carnitine promotes lipid metabolism, stimulating energy production. These three molecules are loaded into liposomes for their effective transdermal delivery. Daily topical applications of the lotions resulted in a hair count that significantly increased for women and marginally increased for men after 6 months of treatment. Furthermore, significant increase in anagen hair and a significant decrease in telogen hair were observed starting from 3 months in male and 1 month in female patients. Thus, the formulations under investigation were effective in attenuating androgenic alopecia-related hair loss in men and women.

Nanodesign of new self-assembling core-shell gellan-transfersomes loading baicalin and in vivo evaluation of repair response in skin.

Gellan nanohydrogel and phospholipid vesicles were combined to incorporate baicalin in new self-assembling core-shell gellan-transfersomes obtained by an easy, scalable method. The vesicles were small in size (~107 nm) and monodispersed (P.I. ≤ 0.24), forming a viscous system (~24 mPa/s) as compared to transfersomes (~1.6 mPa/s), as confirmed by rheological studies. Gellan was anchored to the bilayer domains through cholesterol, and the polymer chains were distributed onto the outer surface of the bilayer, thus forming a core-shell structure, as suggested by SAXS analyses. The optimal carrier ability of core-shell gellan-transfersomes was established by the high deposition of baicalin in the skin (~11% in the whole skin), especially in the deeper tissue (~8% in the dermis). Moreover, their ability to improve baicalin efficacy in anti-inflammatory and skin repair tests was confirmed in vivo in mice, providing the complete skin restoration and inhibiting all the studied inflammatory markers.

Antimalarial Activity of Orally Administered Curcumin Incorporated in Eudragit®-Containing Liposomes.

Curcumin is an antimalarial compound easy to obtain and inexpensive, having shown little toxicity across a diverse population. However, the clinical use of this interesting polyphenol has been hampered by its poor oral absorption, extremely low aqueous solubility and rapid metabolism. In this study, we have used the anionic copolymer Eudragit® S100 to assemble liposomes incorporating curcumin and containing either hyaluronan (Eudragit-hyaluronan liposomes) or the water-soluble dextrin Nutriose® FM06 (Eudragit-nutriosomes). Upon oral administration of the rehydrated freeze-dried nanosystems administered at 25/75 mg curcumin·kg−1·day−1, only Eudragit-nutriosomes improved the in vivo antimalarial activity of curcumin in a dose-dependent manner, by enhancing the survival of all Plasmodium yoelii-infected mice up to 11/11 days, as compared to 6/7 days upon administration of an equal dose of the free compound. On the other hand, animals treated with curcumin incorporated in Eudragit-hyaluronan liposomes did not live longer than the controls, a result consistent with the lower stability of this formulation after reconstitution. Polymer-lipid nanovesicles hold promise for their development into systems for the oral delivery of curcumin-based antimalarial therapies.

Functional response of novel bioprotective poloxamer-structured vesicles on inflamed skin.

Resveratrol and gallic acid, a lipophilic and a hydrophilic phenol, were co-loaded in innovative, biocompatible nanovesicles conceived for ensuring the protection of the skin from oxidative- and inflammatory-related affections. The basic vesicles, liposomes and glycerosomes, were produced by a simple, one-step method involving the dispersion of phospholipid and phenols in water or water/glycerol blend, respectively. Liposomes and glycerosomes were modified by the addition of poloxamer, a stabilizer and viscosity enhancer, thus obtaining viscous or semisolid dispersions of structured vesicles. The vesicles were spherical, unilamellar and small in size (~70 nm in diameter). The superior ability of the poloxamer-structured vesicles to promote the accumulation of both phenols in the skin was demonstrated, as well as their low toxicity and great ability to protect fibroblasts from chemically-induced oxidative damage. The in vivo administration of the vesicular phenols on TPA (phorbol ester)-exposed skin led to a significant reduction of oedema and leukocyte infiltration.

Phycocyanin-encapsulating hyalurosomes as carrier for skin delivery and protection from oxidative stress damage.

The phycobiliprotein phycocyanin, extracted from Klamath algae, possesses important biological properties but it is characterized by a low bioavailability due to its high molecular weight. To overcome the bioavailability problems, phycocyanin was successfully encapsulated, using an environmentally-friendly method, into hyalurosomes, a new kind of phospholipid vesicles immobilised with hyaluronan sodium salt by the simple addition of drug/sodium hyaluronate water dispersion to phospholipids. Liposomes were used as a comparison. Vesicles were small in size and homogeneously dispersed, being the mean size always smaller than 150 nm and PI never higher than 0.31. Liposomes were unilamellar and spherical, the addition of the polymer slightly modify the vesicular shape which remain spherical, while the addition of PEG improve the lamellarity of vesicles being multilamellar vesicles. In all cases phycocyanin was encapsulated in good amount especially using hyalurosomes and PEG hyalurosomes (65 and 61% respectively). In vitro penetration studies suggested that hyalurosomes favoured the phycocyanin deposition in the deeper skin layers probably thanks to their peculiar hyaluronan-phospholipid structure. Moreover, hyalurosomes were highly biocompatible and improved phycocyanin antioxidant activity on stressed human keratinocytes respect to the drug solution.

Effects of ethanol and diclofenac on the organization of hydrogenated phosphatidylcholine bilayer vesicles and their ability as skin carriers.

In this study, the effects of ethanol and/or diclofenac on vesicle bilayer structure have been studied. Liposomes with hydrogenated soy phosphatidylcholine, cholesterol and two different concentrations of diclofenac sodium (5 and 10 mg/ml) were obtained. In addition, ethanol was mixed in the water phase at different concentrations (5, 10 and 20 % v/v) to obtain ethosomes. To characterize vesicles, rehological analysis were carried out to investigate the intervesicle interactions, while bilayer structure was evaluated by small- and wide-angle X-ray scattering. Finally, the ethanol and/or diclofenac concentration-dependent ability to improve diclofenac skin delivery was evaluated in vitro. The addition of 20 % ethanol and/or diclofenac led to solid-like ethosome dispersion due to the formation of a new intervesicle structure, as previously found in transcutol containing vesicle dispersions. However, when using 5-10 % of ethanol the induction to form vesicle interconnections was less evident but the simultaneous presence of the drug at the highest concentration facilitated this phenomenon. Ethosomes containing the highest amount of both, drug (10 mg/ml) and ethanol (20 % v/v), improved the drug deposition in the skin strata and in the receptor fluid up to 1.5-fold, relative to liposomes. Moreover this solid-like formulation can easily overcome drawbacks of traditional liquid liposome formulations which undergo a substantial loss at the application site.

Beclomethasone loaded liposomes enriched with mucin: A suitable approach for the control of skin disorders.

Inflammatory skin disorders are the fourth leading cause of chronic non-fatal conditions, which have a serious impact on the patient quality of life. Due to their treatment with conventional corticosteroids, which often result in poor therapeutic efficacy, relapses and systemic side effects from prolonged therapy, these diseases represent a global burden that negatively impacts the global economy. To avoid these problems and optimize corticosteroid benefits, beclomethasone was loaded into liposome formulations specifically tailored for skin delivery. These formulations were enhanced with mucin (0.1 and 0.5 % w/v) to further ensure prolonged formulation permanence at the site of application. The addition of 0.5 % w/v mucin resulted in the formation of small unilamellar vesicles and multicompartment vesicles. Liposomes and 1mucin-liposomes were smaller (∼48 and ∼61 nm, respectively) and more monodispersed (PI ∼ 0.14 and ∼ 0.17, respectively) than 5mucin-liposomes, which were larger (∼137 nm), slightly polydispersed (PI ∼ 0.23), and less stable during storage (4 months in the dark at 25 °C). Liposomes were negatively charged (∼ -79 mV) irrespective of their composition, and capable of incorporating high amount of beclomethasone (∼ 80 %). In vitro studies on skin fibroblasts and keratinocytes confirmed the high biocompatibility of all formulations (viability ≥ 95 %). However, the use of mucin-liposomes resulted in higher efficacy against nitric oxide production and free radical damage. Finally, topical applications using 12-O-tetradecanoylphorbol-13-acetate-injured skin in vivo experiments showed that only the mucin-enriched formulations could restore healthy conditions within 4 days, underscoring promise as a treatment for skin disorders.

From Field to Waste Valorization: A Preliminary Study Exploring the Impact of the Wine Supply Chain on the Phenolic Profile of Three Sardinian Pomace Extracts.

The winemaking process generates an annual global production of about 10 million tons of waste consisting of stalks, skin, and seeds. The possible reutilization of wine pomace is strictly linked to its chemical composition. In this preliminary study, three different Sardinian white grapes (Malvasia, Vermentino and Nasco) grown in the same area were evaluated through a whole wine production chain. To reduce environmental impact, all the grapes were treated following the integrated production practice (IPP) strategies. The adopted agronomic methods and the main physico-chemical parameters of the fresh fruits and musts were evaluated. A fully qualitative and quantitative characterization of the phenolic fraction of the pomace extracts was performed by HPLC-DAD after a post-winemaking process. Water and ethanol were utilized as green solvents in the extraction process. Additionally, the entire pomace post-winemaking process was carried out within the winery facilities to reduce energy loss and road transportation. The findings demonstrated that large amounts of beneficial polyphenols are present in pomace extracts, and that the type of grape used, agronomic practices, and winemaking method all influence the quantity and quality of the extracts. The polyphenol concentrations in the Vermentino (28,391.5 ± 7.0 mg/kg) and Malvasia pomace (11,316.3 ± 6.5 mg/kg) were found to be the highest and lowest, respectively.

Improving oral bioavailability and pharmacokinetics of liposomal metformin by glycerolphosphate-chitosan microcomplexation.

The purpose of this study was to develop a new delivery system capable of improving bioavailability and controlling release of hydrophilic drugs. Metformin-loaded liposomes were prepared and to improve their stability surface was coated with chitosan cross-linked with the biocompatible ß-glycerolphosphate. X-ray diffraction, differential scanning calorimetry, as well as rheological analysis were performed to investigate interactions between chitosan and ß-glycerolphosphate molecules. The entrapment of liposomes into the chitosan-ß-glycerolphosphate network was assessed by scanning electron microscopy and transmission electron microscopy. Swelling and mucoadhesive properties as well as drug release were evaluated in vitro while the drug oral bioavailability was evaluated in vivo on Wistar rats. Results clearly showed that, compared to control, the proposed microcomplexes led to a 2.5-fold increase of metformin T(max) with a 40% augmentation of the AUC/D value.

Analysis of complementarities between nanomedicine and phytodrugs for the treatment of malarial infection.

The use of nanocarriers in medicine, so-called nanomedicine, is one of the most innovative strategies for targeting drugs at the action site and increasing their activity index and effectiveness. Phytomedicine is the oldest traditional method used to treat human diseases and solve health problems. The recent literature on the treatment of malaria infections using nanodelivery systems and phytodrugs or supplements has been analyzed. For the first time, in the present review, a careful look at the considerable potential of nanomedicine in promoting phytotherapeutic efficacy was done, and its key role in addressing a translation through a significant reduction of the current burden of malaria in many parts of the world has been underlined.

Plants hide an incredible treasure chest of beneficial substances within them. These natural substances have a wide range of beneficial applications for human health, from nutrition to personal care, including the treatment of diseases such as malaria. However, to exploit the full potential of these substances, an innovative approach is needed, and nanomedicine promises that. Nanomedicine involves the use of nanosystems, incredibly small systems, invisible to the naked eye, but their impact is enormous. Thus, bioactive compounds in plants that may have beneficial effects on human health can be placed within these nanosystems to improve their effectiveness. This synergy between nature and nanotechnology offers new opportunities to improve health and well-being, demonstrating how valuable science and technology are in exploring the natural world. After examining the key advantages of nanosystems, this review focuses on some of the earliest antimalarials used and then looks at newer and more promising ones, starting with quinine, extracted from Cinchona bark; moving to the discovery of artemisinin, obtained from Artemisia annua and its derivatives; and ending with an analysis of alternative natural molecules with antimalarial activity. This review examines how nanomedicine can make natural plant-based treatments more effective in fighting malaria. This could help reduce the impact of malaria in many places around the world.

Liposome-based vaccines for minimally or noninvasive administration: an update on current advancements.

INTRODUCTION: Vaccination requires innovation to provide effective protection. Traditional vaccines have several drawbacks, which can be overcome with advanced technologies and different administration routes. Over the past 10 years, a significant amount of research has focussed on the delivery of antigens into liposomes due to their dual role as antigen-carrying systems and vaccine adjuvants able to increase the immunogenicity of the carried antigen. AREAS COVERED: This review encompasses the progress made over the last 10 years with liposome-based vaccines designed for minimally or noninvasive administration, filling the gaps in previous reviews and providing insights on composition, administration routes, results achieved, and Technology Readiness Level of the most recent formulations. EXPERT OPINION: Liposome-based vaccines administered through minimally or noninvasive routes are expected to improve efficacy and complacency of vaccination programs. However, the translation from lab-scale production to large-scale production and collaborations with hospitals, research centers, and companies are needed to allow new products to enter the market and improve the vaccination programs in the future.

Centella asiatica extract-SiO2 nanocomposite: More than a drug-delivery system for skin protection from oxidative damage.

An innovative nanotechnology-based approach was used for the preparation of Centella asiatica (C. asiatica) extract-SiO2 nanocomposites, specifically tailored for skin protection from oxidative damage. Different amounts of C. asiatica glycolic extract (1.0, 3.0, 5.0, and 10.0 wt %) and fumed silica were used to prepare the nanocomposites by means of ball milling method. The influence of both composition of the starting mixture and milling time on the final products was evaluated by different techniques such as X-ray powder diffraction, scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, and nitrogen sorption analysis. Results confirmed the integrity of the natural extract after the milling process, and its successful loading in the silica matrix. No cytotoxicity was observed for the obtained nanocomposites, which showed high in-vitro ability to scavenge 2,2-diphenyl-1-picrylhydrazyl and to protect human keratinocytes from damages induced with hydrogen peroxide.

Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections.

Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around -8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.

A Cocktail-Based Formula for the Design of Nanosized Cosmeceuticals as Skincare and Anti-Age Products.

Nasco and Bovale grape pomace extracts, alone or in association, were loaded in nanoemulsions tailored for cosmetic application, using Kolliphor®RH40 (kolliphor) as the synthetic surfactant, Olivem®1000 (olivem) as the natural one, and lecithin as the cosurfactant. Pink transparent or milky dispersions, as a function of the used extract and surfactant, were obtained to be used as cosmeceutical serum or milk. The sizes of the nanoemulsion droplets were small (≈77 nm with kolliphor and ≈141 nm with olivem), homogenously dispersed (~0.24 with kolliphor and ~0.16 with olivem), highly negatively charged (≈-43 mV irrespective of the used surfactant) and their stability either on storage or under stressing conditions was affected by the used extract and surfactant. Formulations protected the extracts from the degradation caused by UV exposition, were biocompatible against keratinocytes, protected them against oxidative damages induced using hydrogen peroxide and inhibited the release of nitrite induced in macrophages using the lipopolysaccharide inflammatory stimulus. The overall results underlined the key role played by the composition of the formula to achieve a suitable cosmeceutical for skin care but even for the prevention of premature aging and chronic damages caused by the stressing conditions.

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.

Bridging biotechnology and nanomedicine to produce biogreen whey-nanovesicles for intestinal health promotion.

New intestinal health-promoting biotechnological nanovesicles were manufactured by combining the main environmental pollutant generated from the cheese-making process, whey, with phospholipid, sodium hyaluronate and dextrin, thus overcoming environmental and medical challenges. An efficient, consolidated and eco-friendly preparation method was employed to manufacture the vesicles and the bioactive whey was obtained by mesophilic dark fermentation without external inoculum through a homolactic pathway, which was operated in such a way as to maximize the production of lactic acid. The biotechnological nutriosomes and hyalonutriosomes were relatively small (∼100 nm) and characterized by the net negative surface charge (>-30 mV). The addition of maltodextrin to the liposomes and especially to the hyalurosomes significantly stabilized the vesicles under acidic conditions, simulating the gastric environment, as their size and polydispersity index were significantly lower (p < 0.05) than those of the other formulations. The vesicles were effectively internalized by Caco-2 cells and protected them against oxidative stress. Nutriosomes promoted the proliferation of Streptococcus salivarius, a human commensal bacterium, to a better extent (p < 0.05) than liposomes and hyalurosomes, as a function of the concentration tested. These findings could open a new horizon in intestinal protection and health promotion by integrating biotechnology, nanomedicine, sustainability principles and bio-circular economy.