Tempranillo grape extract in transfersomes: A nanoproduct with antioxidant activity

Polyphenols are gaining increasing interest due to their beneficial properties to human health. Grape pomace, the by-product of wine production, is a source of these bioactive compounds. An extract from Tempranillo grape pomace was obtained and characterized qualitatively and quantitatively. The major components found were anthocyanins, flavan-3-ols, and flavonols. To improve the bioavailability of these compounds, the extract was formulated in phospholipid vesicles, namely transfersomes. Spherical unilamellar vesicles around 100 nm each were obtained. The antioxidant activity of both the extract and the transfersomes was evaluated by using colorimetric assays (i.e., DPPH, FRAP, and Folin–Ciocalteu). The cells’ viability and the antioxidant activity were assessed in keratinocytes. The results showed that the extract and the transfersomes had no cytotoxic effects and exerted remarkable antioxidant activity, which was more evident in a vesicle formulation. These findings highlighted the potential of the Tempranillo grape pomace extract and the efficacy of the incorporation into phospholipid vesicles.Fil: Asensio Regalado, Carlos. Universidad del País Vasco; EspañaFil: Alonso Salces, Rosa Maria. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Gallo, Blanca. Universidad del País Vasco; EspañaFil: Berrueta, Luis A.. Universidad del País Vasco; EspañaFil: Era, Benedetta. Università Degli Studi Di Cagliari.; ItaliaFil: Pintus, Francesca. Università Degli Studi Di Cagliari.; ItaliaFil: Caddeo, Carla. Università Degli Studi Di Cagliari.; Itali

Liposome-Mediated Inhibition of Inflammation by Hydroxycitrate

Hydroxycitrate (HCA), a main organic acid component of the fruit rind of Garcinia cambogia, is a natural citrate analog that can inhibit the ATP citrate lyase (ACLY) enzyme with a consequent reduction of inflammatory mediators (i.e., nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2)) levels. Therefore, HCA has been proposed as a novel means to prevent, treat, and ameliorate conditions involving inflammation. However, HCA presents a low membrane permeability, and a large quantity is required to have a biological effect. To overcome this problem, HCA was formulated in liposomes in this work, and the enhancement of HCA cell availability along with the reduction in the amount required to downregulate NO, ROS, and PGE2 in macrophages were assessed. The liposomes were small in size (~60 nm), monodispersed, negatively charged (−50 mV), and stable on storage. The in vitro results showed that the liposomal encapsulation increased by approximately 4 times the intracellular accumulation of HCA in macrophages, and reduced by 10 times the amount of HCA required to abolish LPS-induced NO, ROS, and PGE2 increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes

Liposome-Mediated Delivery Improves the Efficacy of Lisosan G against Retinopathy in Diabetic Mice

Nutraceuticals are natural substances whose anti-oxidant and anti-inflammatory properties may be used to treat retinal pathologies. Their efficacy is limited by poor bioavailability, which could be improved using nanocarriers. Lisosan G (LG), a fermented powder from whole grains, protects the retina from diabetic retinopathy (DR)-induced damage. For this study, we tested whether the encapsulation of LG in liposomes (LipoLG) may increase its protective effects. Diabetes was induced in mice via streptozotocin administration, and the mice were allowed to freely drink water or a water dispersion of two different doses of LG or of LipoLG. Electroretinographic recordings after 6 weeks showed that only the highest dose of LG could partially protect the retina from diabetes-induced functional deficits, while both doses of LipoLG were effective. An evaluation of molecular markers of oxidative stress, inflammation, apoptosis, vascular endothelial growth factor, and the blood-retinal barrier confirmed that the highest dose of LG only partially protected the retina from DR-induced changes, while virtually complete prevention was obtained with either dose of LipoLG. These data indicate that the efficacy of LG in contrasting DR is greatly enhanced by its encapsulation in liposomes and may lay the ground for new dietary supplements with improved therapeutic effects against DR

Immunometabolism Modulation by Extracts from Pistachio Stalks Formulated in Phospholipid Vesicles

Several studies have demonstrated the effectiveness of plant extracts against various diseases, especially skin disorders; namely, they exhibit overall protective effects. The Pistachio (Pistacia vera L.) is known for having bioactive compounds that can effectively contribute to a person’s healthy status. However, these benefits may be limited by the toxicity and low bioavailability often inherent in bioactive compounds. To overcome these problems, delivery systems, such as phospholipid vesicles, can be employed. In this study, an essential oil and a hydrolate were produced from P. vera stalks, which are usually discarded as waste. The extracts were characterized by liquid and gas chromatography coupled with mass spectrometry and formulated in phospholipid vesicles intended for skin application. Liposomes and transfersomes showed small size (<100 nm), negative charge (approximately −15 mV), and a longer storage stability for the latter. The entrapment efficiency was determined via the quantification of the major compounds identified in the extracts and was >80%. The immune-modulating activity of the extracts was assayed in macrophage cell cultures. Most interestingly, the formulation in transfersomes abolished the cytotoxicity of the essential oil while increasing its ability to inhibit inflammatory mediators via the immunometabolic citrate pathway

Liposomal Formulations to Improve Antioxidant Power of Myrtle Berry Extract for Potential Skin Application

Many substances in plant extracts are known for their biological activities. These substances act in different ways, exerting overall protective effects against many diseases, especially skin disorders. However, plant extracts’ health benefits are often limited by low bioavailability. To overcome these limitations, drug delivery systems can be employed. In this study, we evaluated the antioxidant power of an ethanolic extract from Myrtus communis L. (myrtle) berries through colorimetric tests (DPPH and FRAP). The antioxidant activity was also verified by using fibroblast cell culture through cellular Reactive Oxygen Species (ROS) levels measurements. Moreover, the myrtle extract was formulated in phospholipid vesicles to improve its bioavailability and applicability. Myrtle liposomes were characterized by size, surface charge, storage stability, and entrapment efficiency; visualized by using cryo-TEM images; and assayed for cytocompatibility and anti-ROS activity. Our results suggest that myrtle liposomes were cytocompatible and improved the extract’s antioxidant power in fibroblasts, suggesting a potential skin application for these formulations and confirming that nanotechnologies could be a valid tool to enhance plant extracts’ potentialities

Co-Loading of Ascorbic Acid and Tocopherol in Eudragit-Nutriosomes to Counteract Intestinal Oxidative Stress

The present study aimed at developing a new vesicular formulation capable of promoting the protective effect of ascorbic acid and tocopherol against intestinal oxidative stress damage, and their efficacy in intestinal wound healing upon oral administration. A pH-dependent copolymer (Eudragit® L100), a water-soluble prebiotic fibre (Nutriose® FM06), a phospholipid mixture (Lipoid S75), and two natural antioxidants (ascorbic acid and tocopherol) were combined to fabricate eudragit-nutriosomes by a simple, solvent-free procedure. The vesicles were spherical and oligolamellar, with some multicompartment structures in Eudragit-nutriosomes, small in size (~100 nm), with highly negative zeta potential. The effect of Eudragit® and Nutriose® on the stability on storage and in simulated gastrointestinal fluids were confirmed by the Turbiscan® technology and in vitro studies, respectively. Eudragit-nutriosomes exhibited a protective effect against H2O2-induced oxidative stress, and a proliferative effect in Caco-2 cells, as they provided the closure of the scratched area after 96 h of incubation. Keywords: Eudragit, Nutriose, phospholipid vesicles, antioxidant, intestinal wound healin

Effect of liposomal formulation of ascorbic acid on corneal permeability

Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues

New Insight on the Bioactivity of Solanum aethiopicum Linn. Growing in Basilicata Region (Italy): Phytochemical Characterization, Liposomal Incorporation, and Antioxidant Effects

Food extract’s biological effect and its improvement using nanotechnologies is one of the challenges of the last and the future decades; for this reason, the antioxidant effect of scarlet eggplant extract liposomal incorporation was investigated. Scarlet eggplant (Solanum aethiopicum L.) is a member of the Solanaceae family, and it is one of the most consumed vegetables in tropical Africa and south of Italy. This study investigated the antioxidant activity and the phytochemical composition of S. aethiopicum grown in the Basilicata Region for the first time. The whole fruit, peel, and pulp were subjected to ethanolic exhaustive maceration extraction, and all extracts were investigated. The HPLC-DAD analysis revealed the presence of ten phenolic compounds, including hydroxycinnamic acids, flavanones, flavanols, and four carotenoids (one xanthophyll and three carotenes). The peel extract was the most promising, active, and the richest in specialized metabolites; hence, it was tested on HepG2 cell lines and incorporated into liposomes. The nanoincorporation enhanced the peel extract’s antioxidant activity, resulting in a reduction of the concentration used. Furthermore, the extract improved the expression of endogenous antioxidants, such as ABCG2, CAT, and NQO1, presumably through the Nrf2 pathway

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

im: 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

PEGylated Liposomes Loaded with Carbamate Inhibitor ANP0903 Trigger Apoptosis by Enhancing ER Stress in HepG2 Cancer Cells

Liver cancer is one of the most common causes of cancer death worldwide. In recent years, substantial progress has been made in the development of systemic therapies, but there is still the need for new drugs and technologies that can increase the survival and quality of life of patients. The present investigation reports the development of a liposomal formulation of a carbamate molecule, reported as ANP0903, previously tested as an inhibitor of HIV-1 protease and now evaluated for its ability to induce cytotoxicity in hepatocellular carcinoma cell lines. PEGylated liposomes were prepared and characterized. Small, oligolamellar vesicles were produced, as demonstrated by light scattering results and TEM images. The physical stability of the vesicles in biological fluids was demonstrated in vitro, alongside the stability during storage. An enhanced cellular uptake was verified in HepG2 cells treated with liposomal ANP0903, resulting in a greater cytotoxicity. Several biological assays were performed to elucidate the molecular mechanisms explaining the proapoptotic effect of ANP0903. Our results allow us to hypothesize that the cytotoxic action in tumor cells is probably due to the inhibition of the proteasome, resulting in an increase in the amount of ubiquitinated proteins within the cells, which in turn triggers activation of autophagy and apoptosis processes, resulting in cell death. The proposed liposomal formulation represents a promising approach to deliver a novel antitumor agent to cancer cells and enhance its activity