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.

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.

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.

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.

Extraction, Characterization and Incorporation of Hypericum scruglii Extract in Ad Hoc Formulated Phospholipid Vesicles Designed for the Treatment of Skin Diseases Connected with Oxidative Stress.

An extract of Hypericum scruglii, an endangered endemic plant of Sardinia (Italy), was prepared and characterized. It was loaded in special phospholipid vesicles, glycerosomes, which were modified by adding maltodextrin (glucidex) and a polymer (gelatin or hyaluronan). The corresponding liposomes were also prepared and used as reference. The vesicles disclosed suitable physicochemical features for skin delivery. Indeed, their mean diameter ranged from 120 to 160 nm, they were homogeneously dispersed (polydispersity index ≤ 0.30), and their zeta potential was highly negative (~-45 mV). The vesicle dispersions maintained unchanged characteristics during 60 days of storage, were highly biocompatible, and were able to protect keratinocytes against damages due to oxidative stress induced by treating them with hydrogen peroxide. Vesicles were also capable of promoting cell proliferation and migration in vitro by means of a scratch wound assay. The results confirmed the fruitful delivery of the extract of H. scruglii in glycerosomes modified with glucidex and gelatin and their promising ability for skin protection and treatment.

Entrapment of Citrus limon var. pompia Essential Oil or Pure Citral in Liposomes Tailored as Mouthwash for the Treatment of Oral Cavity Diseases.

This work aimed at developing a mouthwash based on liposomes loading Citrus limon var. pompia essential oil or citral to treat oropharyngeal diseases. Vesicles were prepared by dispersing phosphatidylcholine and pompia essential oil or citral at increasing amounts (12, 25 and 50 mg/mL) in water. Transparent vesicle dispersions were obtained by direct sonication avoiding the use of organic solvents. Cryogenic transmission electron microscopy (cryo-TEM) confirmed the formation of unilamellar, spherical and regularly shaped vesicles. Essential oil and citral loaded liposomes were small in size (~110 and ~100 nm, respectively) and negatively charged. Liposomes, especially those loading citral, were highly stable as their physico-chemical properties did not change during storage. The formulations were highly biocompatible against keratinocytes, were able to counteract the damages induced in cells by using hydrogen peroxide, and able to increase the rate of skin repair. In addition, liposomes loading citral at higher concentrations inhibited the proliferation of cariogenic bacterium.

Innovative strategies to treat skin wounds with mangiferin: fabrication of transfersomes modified with glycols and mucin.

Aim: The moisturizing properties of glycerol, the penetration enhancing capability of propylene glycol and the bioadhesive properties of mucin were combined to improve the carrier capabilities of transfersomes and the efficacy of mangiferin in the treatment of skin lesions. Materials & methods: Mangiferin was incorporated in transfersomes and glycoltransfersomes, which were also modified with mucin. The physico-chemical features were assessed, along with the efficacy against oxidative stress and skin wounds in vitro and in vivo. Results: Glycoltransfersomes promoted the deposition of mangiferin in epidermis and dermis, protected fibroblasts from oxidative stress and stimulated their proliferation. The wound healing and anti-inflammatory efficacy of glycoltransfersomes were confirmed in vivo. Conclusion: Results confirmed the potential of glycoltransfersomes in preventing/treating of skin lesions.

Comparison between Citral and Pompia Essential Oil Loaded in Phospholipid Vesicles for the Treatment of Skin and Mucosal Infections.

Citrus species extracts are well known sources of bio-functional compounds with health-promoting effects. In particular, essential oils are known for their antibacterial activity due to the high content of terpenes. In this work, the steam-distilled essential oil from the leaves of Citrus limon var. pompia was loaded in phospholipid vesicles. The physico-chemical characteristics of the essential oil loaded vesicles were compared with those of vesicles that were loaded with citral, which is one of the most abundant terpenes of Citrus essential oils. The biocompatibility of the vesicles was assessed in vitro in human keratinocytes. Furthermore, the antimicrobial activity of the vesicles was tested while using different bacterial strains and a yeast: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, respectively. The vesicles were small in size (~140 nm), slightly polydispersed (PI ~ 0.31), highly negatively charged (~ -73 mV), and able to incorporate high amounts of essential oil or citral (E% ~ 86%). Pompia essential oil and citral exhibited antimicrobial activity against all of the assayed microorganisms, with P. aeruginosa being the least sensitive. Citral was slightly more effective than pompia essential oil against E. coli, S. aureus, and C. albicans. The incorporation of citral in vesicles improved its antifungal activity against C. albicans.