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The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography-mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (-13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage.

Plant-derived products have been used for preventive and curative purposes from the ancient era to the present day. Several studies have demonstrated the efficacy of either multicomponent-based extracts, enriched fractions, or isolated bioactives. However, they often display low solubility and bioavailability, chemical instability, poor absorption, and even toxicity, which restrict application in therapy. The use of drug delivery systems, especially nanocarriers, can overcome these physicochemical and pharmacokinetic limitations. In this study, an extract from Onopordum illyricum leaves was produced by maceration in 80% ethanol, characterized by liquid chromatography coupled to mass spectrometry, and formulated in phospholipid vesicles with the aim of exploiting and possibly enhancing its bioactivity for skin delivery. The results showed that phenolic compounds were abundantly present in the extract, especially hydroxycinnamic acid and flavonol derivatives. The extract-loaded vesicles showed small size (<100 nm), high entrapment efficiency (even >90% for most phenolic compounds), and good long-term stability. Moreover, the extract-loaded vesicles exhibited remarkable antioxidant activity, as demonstrated by colorimetric assays and by enhanced reduction of intracellular reactive oxygen species (ROS) levels in cultured skin cells. Hence, our findings support the key role of nanotechnological approaches to promote the potential of plant extracts and strengthen their application in therapy.

Ellagic acid (EA) has long been recognized as a very active antioxidant, anti-inflammatory, and antimicrobial agent. However, its low bioavailability has often hampered its applications in health-related fields. Here, we report a phospholipid vesicle-based controlled release system for EA, involving the exploitation of chestnut wood mud (CWM), an industrial by-product from chestnut tannin production, as a largely available and low-cost source of this compound. Two kinds of CWM with different particle size distributions, indicated as CWM-A and CWM-B (<100 and 32 µm, respectively), containing 5 ± 1% w/w EA, were incorporated into transfersomes. The latter were small in size (~100 nm), homogeneously dispersed, and negatively charged. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays indicated up to three-fold improvement in the antioxidant properties of CWM upon incorporation into transfersomes. The kinetics of EA released under simulated physiological conditions were evaluated by UV-Vis spectroscopy and HPLC analysis. The best results were obtained with CWM-B (100% of EA gradually released after 37 days at pH 7.4). A stepwise increase in the antioxidant properties of the released material was also observed. Cell-based experiments confirmed the efficacy of CWM-B transfersomes as antioxidant agents in contrasting photodamage.

Plant extracts have long served as important sources of bioactive compounds, and they are currently the focus of extensive research in the development of novel preventive and therapeutic strategies. However, their health benefits are often limited by low bioavailability. Nanoparticle delivery systems can represent a solution to such limitations. Euphorbia characias is a Mediterranean shrub known to have biological activities, such as inhibiting tyrosinase and showing a potential role as a skin-whitening agent. In this study, an ethanolic extract from E. characias leaves was tested for its inhibitory activity on skin-related enzymes, such as elastase, collagenase, and hyaluronidase, and for sun protection factors. Moreover, the extract was formulated in phospholipid vesicles to improve its local bioavailability and applicability. The vesicles were characterized by size, surface charge, storage stability, and entrapment efficiency. The nanoformulation was also evaluated for antioxidant activity and assayed for cytocompatibility and anti-tyrosinase activity in melanoma cells. Our findings demonstrated that the extract has a photo-protective effect and enzyme-inhibitory properties. E. characias nanoformulation was also cytocompatible and improved the extract's activity in the cells, suggesting a potential skin application for antimelanogenic treatments and confirming the key role of nanotechnological approaches to maximize plant extract's potentialities.

Antioxidant compounds with health benefits can be found in food processing residues, such as grape pomace. In this study, antioxidants were identified and quantified in an extract obtained from Graciano red grape pomace via a green process. The antioxidant activity of the extract was assessed by the DPPH and FRAP tests, and the phenolic content by the Folin-Ciocalteu test. Furthermore, nanotechnologies were employed to produce a safe and effective formulation that would exploit the antioxidant potential of the extract for skin applications. Anthocyanins, flavan-3-ols and flavanols were the main constituents of the grape pomace extract. Phospholipid vesicles, namely liposomes, were prepared and characterized. Cryo-TEM images showed that the extract-loaded liposomes were predominantly spherical/elongated, small, unilamellar vesicles. Light scattering results revealed that the liposomes were small (~100 nm), homogeneously dispersed, and stable during storage. The non-toxicity of the liposomal formulation was demonstrated in vitro in skin cells, suggesting its possible safe use. These findings indicate that an extract with antioxidant properties can be obtained from food processing residues, and a liposomal formulation can be developed to exploit its bioactive value, resulting in a promising healthy product.

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.

The peppers of the Capsicum species are exploited in many fields, as flavoring agents in food industry, or as decorative and therapeutic plants. Peppers show a diversified phytochemical content responsible for different biological activities. Synergic activity exerted by high levels of antioxidant compounds is responsible for their important anti-inflammatory property. A methanolic extract was obtained from a new pepper genotype and tested for anti-inflammatory activity. The extract was incorporated into phospholipid vesicles to increase the bioavailability of its bioactive components. Two types of phospholipid vesicles were produced, conventional liposomes and Penetration Enhancer containing Vesicles (PEVs). They were tested in human monoblastic leukemia U937 cell line, showing no cytotoxic effect. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels were measured to value the in vitro efficacy of the vesicles in regulating inflammatory responses. Liposomal incorporation significantly reduced ROS levels in extract-treated LPS-activated cells. Furthermore, LC-MS/MS analyses demonstrated that liposomes facilitated the transport of the extract components across the cell membrane and their accumulation into the cytoplasm.

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 E 2 (PGE 2 )) 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 PGE 2 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 PGE 2 increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes.

Overproduction of oxidants in the human body is responsible for oxidative stress, which is associated with several diseases. High intake of vegetables and fruits can reduce the risk of chronic diseases, as they are sources of bioactive compounds capable of contrasting the free radical effects involved in cancer, obesity, diabetes, and neurodegenerative and cardiovascular diseases. Capsicum annuum L. cv Senise is a sweet pepper that is grown in the Basilicata region (Italy). It is an important source of polyphenols, carotenoids, and capsinoids and can play a key role in human health. In this study, an ethanol extract was obtained from C. annuum dried peppers and the analysis of the phytochemical composition was performed by LC-ESI/LTQ Orbitrap/MS. The extract was incorporated into liposomes, which showed small size (~80 nm), good homogeneity, negative surface charge, and good stability in storage. The biological activity of the extract was evaluated in the human hepatoma (HepG2) cell line, used as model cells. The extract showed no cytotoxic activity and reduced the intracellular reactive oxygen species (ROS) level in stressed cells. The antioxidant activity was further improved when the extract was loaded into liposomes. Moreover, the extract promoted the expression of endogenous antioxidants, such as catalase, superoxide dismutase, and glutathione peroxidase through the Nrf-2 pathway evaluated by RT-PCR.

Nowadays, an increasing interest in combinatorial drug delivery systems is emerging, highlighting the possibility of exploiting essential oils (EO) for topical applications. This work aimed at developing nanostructured lipid carriers (NLC) for the combined delivery of ferulic acid and Lavandula EO, whose beneficial effects in wound-healing processes have been widely reported. Homogeneous (polydispersity index, PDI < 0.2) nanoparticles with a small size (<150 nm) and a high encapsulation efficiency (>85%) were obtained. The co-presence of ferulic acid and Lavandula EO, as compared to synthetic isopropyl myristate-based NLC, increased nanoparticles' stability, due to higher ordering chains, as confirmed by morphological and physicochemical studies. An enhanced cytocompatibility was observed when combining ferulic acid and Lavandula EO, as confirmed by in vitro studies on fibroblasts. Furthermore, the combined delivery of ferulic acid and Lavandula EO significantly promoted cell migration with higher effectiveness in respect to the free drug solution and the carrier without the EO. Taken all together, our results suggest a potential combined effect of the antioxidant ferulic acid and Lavandula EO co-delivered in lipid nanoparticles in promoting cell proliferation and migration, representing a promising strategy in the treatment of wounds.

Phytochemicals from Lippia citriodora leaves were extracted by applying an innovative technology based on the use of microwaves, which represents an alternative method to extract bioactive substances. The obtained extract was incorporated into phospholipid vesicles in order to promote the antioxidant effect of the bioactive molecules present in L. citriodora extract. The extract was analyzed by High Performance Liquid Chromatography coupled to Time-Of-Flight mass spectrometer by electrospray (HPLC-ESI-TOF-MS) and different phytochemicals were detected and quantified. The whole extract was incorporated in liposomes, glycerosomes (liposomes modified with glycerol) and propylene glycol-containing vesicles (PG-PEVs). Moreover, a biopolymer obtained from fish by-product, that is Thunnus albacares skin, was added to improve the bioactivity of the formulations. The in vitro biocompatibility and the antioxidant efficacy of the extract in solution or loaded in the vesicles were tested in primary mouse embryonic fibroblasts (3T3). The results showed the superior bioactivity of the vesicle formulations over the aqueous solution of the extract, which points to an interesting strategy for the treatment of skin disorders.

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 .

Background: The nanoincorporation of the extract of Citrus limon (L.) Osbeck var. pompia into liposomes was aimed at improving its antioxidant and antibacterial effects. Methods: The extract of the rind of Citrus limon (L.) Osbeck var. pompia was obtained by maceration in ethanol, evaporation, and freeze-drying. The extract phytochemical fingerprint was obtained by HPLC and mass spectrometry, and it was determined that gallic acid, neohesperidin, eriocitrin, and neoeriocitrin were the most abundant components. The freeze-dried extract was loaded in liposomes, glycerosomes, and penetration-enhancer-containing vesicles prepared with propylene glycol (PG-PEVs). Results: Capability of the vesicles of improving efficacy of the extract in counteracting oxidative stress was studied in vitro in keratinocytes, along with antimicrobial activity against planktonic cultures of Streptococcus mutans , Lactobacillus acidophilus , and Streptococcus sanguinis . Conclusion: Results showed that the vesicles, especially glycerosomes and PG-PEVs, prevented oxidative damage and cell death, and inhibited bacterial proliferation.