The comparative perspective of phytochemistry and biological properties of the Apiaceae family plants.

Despite the availability of numerous reports on the discovery of medicinal plant compounds and their properties, one may encounter contradictory results released by these reports at the level of plant families and even within species. To establish an accurate perspective of the Apiaceae family, this study examined the fruit essential oil and methanolic extract of wild and common species of this family. According to the measurement of the antioxidant property in the methanolic extract of the fruits using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, Ferula gummosa, Pimpinella anisum and Cuminum cyminum have high power in inhibiting free radicals. However, Bunium persicum had the strongest DPPH radicals inhibitory potential among all essential oils. The results of antimicrobial tests and their classification analysis showed that C. cyminum and B. persicum fruit essential oil with a high amount of cuminaldehyde had the most antibacterial properties. At the same time, the antifungal properties of H. persicum essential oil (rich in aliphatic ester) were stronger than those of the all the studied plants. Also, the essential oils of F. gummosa and Kelussia odoratissima had favourable antimicrobial properties compared to other studied plants. The investigation of the bacterial structure by scanning electron microscope confirmed the effect of the applied essential oils dose and their antibacterial potential. In general, for the first time, this paper determined the biological values of the fruit essential oil of some wild plants, such as K. odoratissima and H. persicum. Besides, in vitro examination and the mathematical models provided a suitable classification, which makes a comprehensive view in terms of the properties of the Apiaceae family.

Inhalable Mannosylated Rifampicin-Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy.

Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)-curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.

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.

Complementary effect of Zingiber officinalis extract and citral in counteracting non allergic nasal congestion by simultaneous loading in ad hoc formulated phospholipid vesicles.

Natural nasal spray formulations were prepared by using Zingiber officinalis (Z. officinalis) extract and citral synergically loaded into specifically designed phospholipid vesicles. Phospholipid vesicles were selected according to their stabilizing effect on the nasal mucosal barrier, and their effectiveness was further potentiated by the co-loading of Z. officinalis extract as antioxidant and anti-inflammatory agent, and citral as antibacterial molecule. Cryo-TEM images confirmed the formation of morphologically homogeneous and small vesicles, sized around 100 nm, negatively charged (-44 mV) and highly biocompatible (viability ≥100%) as detected by using epithelial cells. The analysis of size distribution of sprayed droplets, average velocity module and spray cone angle suggested a good aptitude of the vesicles to be nebulized and their effective deposition in the nasal cavity. Moreover, vesicles were effectively capable of inhibiting some nasal pathogenic bacteria (i.e. Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli) and to protect the epithelial cells against oxidative damage. The formulations are natural and safe, and all of them have shown promising technological and biological properties suggesting their possible application in the nasal cavity for the treatment of congestions and non-allergic rhinitis.

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.

Combination of grape extract-silver nanoparticles and liposomes: A totally green approach.

In the present work, silver nanoparticles were prepared using a totally green procedure combining silver nitrate and an extract of grape pomace as a green source. Additionally, nanoparticles were stabilized using phospholipid and water and/or a mixture of water and propylene glycol (PG). To the best of our knowledge, grape-silver nanoparticle stabilized liposomes or PG-liposomes were formulated, for the first time, combining the residual products of wine-made industry, silver nitrate and phospholipids, avoiding the addition of hazardous substances to human health and the environment, in an easy, scalable and reproducible method. The structure and morphology of grape-silver nanoparticle stabilized vesicles were evaluated by transmission electron microscopy (TEM), UV-vis spectroscopy and photon correlation spectroscopy. Samples were designed as possible carrier for skin protection because of their double function: the grape extract acts as antioxidant and the colloidal silver as antimicrobial agent, which might be helpful in eliminating dangerous free radicals and many pathogenic microorganisms. Obtained nanoparticles were small in size and their combination with phospholipids did not hamper the vesicle formation, which were multilamellar and sized ~100nm. TEM images shows a heterogeneous distribution of nanoparticles, which were located both in the intervesicular medium and in the vesicular structure. Further, grape-silver nanoparticles, when stabilized by liposomes, were able to inhibit the proliferation of both Staphylococcus aureus and Pseudomonas aeruginosa and provided a great protection of keratinocytes and fibroblasts against oxidative stress avoiding their damage and death.

Polymer-associated liposomes for the oral delivery of grape pomace extract.

The pomaces from red grapes were used as a source of phenolic antioxidants, which are known to have health-promoting effects. Environmentally-friendly extraction strategies were investigated to improve the rate and recovery of an extract with high phenolic content and antioxidant activity, which were evaluated by the Folin-Ciocalteu, DPPH, ABTS(+), CUPRAC and FRAP assays. The extract was incorporated in liposomes, which were stabilized by the addition of a natural polysaccharide, sodium alginate or arabic gum, widely used in pharmaceutical and food industries as thickeners and stabilizers. Results showed that the polymer-associated liposomes were approximately 300nm in size, spherical in shape, and with high entrapment efficiency. The polymers prevented vesicle degradation in the gastric environment, and played a key role in improving liposomes' performances, especially arabic gum. The polymer-associated liposomes were biocompatible and protected Caco-2 cells against oxidative stress. The achieved results suggest a potential application of the polymer-associated liposomes loaded with the grape pomace extract in the nutraceutical field.

Chemical characterization of Citrus limon var. pompia and incorporation in phospholipid vesicles for skin delivery.

The components of pompia, a hybrid Citrus species cultivated only in Sardinia (Italy), were extracted using an environmentally-friendly method and food-grade solvents. Taking into account that only few data are available on pompia composition, the phytochemical fingerprint of its rind extract was obtained by accurate component separation and identification, combining HPLC and mass spectrometry. Different flavones such as naringin (23.77µg/mg), neoeriocitrin (46.53µg/mg) and neohesperidin (44.57µg/mg) were identified. Additionally, the antioxidant activity and phenolic content were confirmed by DPPH and Folin-Ciocalteu assays. The whole extract was incorporated in innovative phospholipid vesicles, namely glycerosomes, hyalurosomes and glycerol containing hyalurosomes, which were prepared using a high ratio of extract/phospholipid (1/3.5w/w). The in vitro biocompatibility of the nanoincorporated extract and its ability to potentiate the aptitude of the extract to counteract oxidative stress in skin cells were evaluated. The vesicles, especially glycerol containing hyalurosomes, were able to prevent oxidative damage and death of both keratinocytes and fibroblasts, promoting their viability.

Delivery of liquorice extract by liposomes and hyalurosomes to protect the skin against oxidative stress injuries.

Liquorice extract, obtained by percolation in ethanol of Glycyrrhiza glabra L. roots, was incorporated in liposomes and hyalurosomes, new phospholipid-sodium hyaluronate vesicles, and their protective effect against oxidative stress skin damages was probed. As a comparison, raw glycyrrhizin was also tested. All the vesicles were small in size (≤ 100 nm), with a highly negative zeta potential ensuring long-term stability, and able to incorporate a high amount of the extract. In vitro tests showed that the liquorice extract loaded in vesicles was able to scavenge DPPH free radical (80% inhibition) and to protect 3T3 fibroblasts against H2O2-induced oxidative stress, restoring the normal conditions. By contrast, glycyrrhizin showed poor antioxidant activity, and was not able to efficiently counteract the oxidative effect of H2O2. In addition, the incorporation of the liquorice extract into the vesicular systems promoted the proliferation and migration of 3T3 fibroblasts, favouring the closure of the scratched area. In vivo anti-inflammatory tests on mice confirmed the ability of the proposed nanosystems to improve the local efficacy of the extract, favouring the re-epitelization process.

Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation.

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30-49 nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers.