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.

Topiramate pharmacokinetics in neonates undergoing therapeutic hypothermia and proposal of an optimised dosing schedule.

AIM: The adequate dosing of topiramate in neonates undergoing therapeutic hypothermia has not been established. The aim of this study was to design a dosing schedule capable of providing topiramate serum concentrations within the accepted therapeutic range. METHODS: Neonates (n = 52) with hypoxic ischaemic encephalopathy and subjected to therapeutic hypothermia were dosed with topiramate, 5 mg/kg on day one and 3 mg/kg on days two to five, to decrease seizure events. A total of 451 topiramate serum concentrations obtained in the patients were used to develop a population pharmacokinetic model using a non-linear mixed-effects modelling approach. RESULTS: A one-compartment model with first-order absorption and two different clearance terms, one for the cooling period and another for the post-warming period, were used to describe the concentration-time topiramate data. The probability of no-seizure events could not be related to topiramate concentrations, which was attributed to excessively low topiramate concentrations. A modified dosage schedule was designed with the aim of obtaining more than 90% of patients with topiramate concentrations within the therapeutic range after the first dose. CONCLUSION: The dosage schedule of topiramate in these patients should be modified with the aim of decreasing the frequency of seizure events.

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.

Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.

Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-EFV). In vivo studies showed similar increases in the plasma levels of EFV when it was coadministered with SRT or NT. However, the studies using rat hepatic microsomes showed a more potent inhibitory effect of NT than of SRT on the metabolism of EFV, with values for the 50% inhibition constant (IC50) and inhibitory constant (Ki) for NT about 9-fold lower than those for SRT. An equation was deduced that explains the similar in vivo effects of SRT and NT in spite of the different in vitro performance data. Using human hepatic microsomes, the strongest inhibitory effect was observed with SRT. In summary, pharmacokinetic interactions between EFV, SRT, and NT, associated with the inhibition of hepatic metabolism of EFV, have been detected in rats. Both antidepressants also inhibit EFV metabolism in human hepatic microsomes, but additional in vivo studies in humans are required to evaluate the clinical implication of this interaction.

Pharmacokinetic interaction between nevirapine and nortriptyline in rats: inhibition of nevirapine metabolism by nortriptyline.

One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found. In vitro studies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT. In vivo human studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP.

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.

Topical delivery systems containing clotrimazole for the management of candidiasis: Effect of different excipients and enhanced antifungal activity of nanovesicles.

WHO classified Candida albicans as one of the four critical priority fungi for public health worldwide in 2022. Conventional topical formulations commercially available for the treatment of cutaneous candidiasis are associated with low drug bioavailability at the infection site and the lack of a sustained therapeutic effect. The main objectives of this work were to develop new topical administration systems of clotrimazole (CLT) and study the influence of surfactants on the antifungal inhibitory efficacy. Therefore, the minimum concentration of CLT required to inhibit 50 % of growth (MIC50) was determined, obtaining a value of approximately 15 ng/mL. A non-ionic emulsion type 1, Beeler base cream, hydrogel and liposomes containing CLT were designed, prepared, characterized and their antifungal activity against C. albicans was tested. CLT loaded liposomes were small in size (102 nm), homogeneous (polydispersity index = 0.3) and uncharged (+0.07 mV), showing higher antifungal activity against C. albicans than that of the commercially available cream Canesten®. Furthermore, the antifungal activity of CLT was reduced in combination with surfactants such as Tween-80/Span-80 or Brij-S10. Sodium lauryl sulphate showed a fungicidal effect that disappeared when formulated as part of the Beeler base cream.

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.

Determination of sertraline in rat plasma by HPLC and fluorescence detection and its application to in vivo pharmacokinetic studies.

A simple, rapid, and sensitive HPLC method based on 9H-fluoren-9-ylmethyl chloroformate derivatization for the quantification of sertraline in rat plasma has been developed, requiring a plasma sample of only 0.1 mL, which was deproteinized and derivatized for 5 min in two single steps. The obtained derivative was stable at room temperature and was determined by HPLC using a fluorescence detector. The analytical column was a C(18) column and the mobile phase was acetonitrile and water (80:20, v/v). Calibration curves were linear in the range of 10-500 ng/mL. The limit of detection was approximately 3 ng/mL, and the lower limit of quantification was established at 10 ng/mL. The bias of the method was lower than 10%, and the within day as well as between day, relative standard deviations were lower than 12%. This analytical method was successfully applied to characterize sertraline pharmacokinetics in rats following intravenous (t(1/2) = 213 ± 48 min, Cl = 43.1 ± 8.7 mL/min, V(d) = 11560 ± 1861 mL) and oral (C(max) = 156 ± 76 ng/mL, t(max) = 63.8 ± 16.3 min) administration of 2 and 5 mg, respectively.

The Usefulness of In Vitro Percutaneous Absorption Experiments Applying the Infinite Dose Technique to Predict In Vivo Plasma Levels: Comparison of Model-Predicted and Observed Plasma Concentrations of Nortriptyline in Rats.

The aims of this study were to evaluate the feasibility of a nortriptyline (NT) formulation for transdermal administration and to assess the usefulness of an estimated kinetic parameter (kout) using the in vitro infinite dose technique to predict in vivo plasma levels when used in combination with pharmacokinetic parameters. To do so, a simple one-compartment model was used to describe the transport of a permeant across a membrane (skin). This model provides relatively simple expressions for the amount of permeant in the skin, the cumulative amount of permeant that crosses the skin, and the flux of permeant, for both the infinite and the finite dose regimens. Transdermal administration of the formulated NT gel to rats resulted in plasma levels of approximately 150 ng/mL between 8 and 30 h post-administration. These levels were higher than the minimum concentration of 40 ng/mL recommended for smoking cessation therapy and slightly higher than the upper limit of the therapeutic range for the treatment of depression in humans. The one-compartment model used to describe transport across the skin was connected to a two-compartment pharmacokinetic model used to predict NT plasma concentrations in rats using the kout determined in vitro and the values of other pharmacokinetic parameters obtained in vivo. The predicted concentrations were close to the observed plasma levels and the time profiles were similar for both types of data. These results show the usefulness of the kout parameter determined in vitro to predict plasma concentrations of drugs administered percutaneously.

Formulation and In Vitro Efficacy Assessment of Teucrium marum Extract Loading Hyalurosomes Enriched with Tween 80 and Glycerol.

The extract of Teucrium marum L. (Lamiaceae) was obtained using the aerial parts of the plant, by means of a maceration process. Verbascoside, caffeic acids derivatives and flavonols were the main components contained in the extract as detected using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) as an analytical method. The extract was successfully incorporated into hyalurosomes, which were further enriched by adding a water cosolvent (glycerol) and a surfactant (Tween 80), thus obtaining glycerohyalurosomes. Liposomes, transfersomes and glycerosomes were prepared as well and used as comparisons. All vesicles were small, as the mean diameter was never higher than ~115 nm, thus ideal for topical application and stable on storage, probably thanks to the highly negative surface charge of the vesicles (~-33 mV). The cryo-TEM images confirmed the formation of close-packed, oligolamellar and multicompartment hyalurosomes and glycerohyalurosomes in which around 95% of the used extract was retained, confirming their ability to simultaneously load a wide range of molecules having different chemical natures. Moreover, the extract, when loaded in hyalurosomes and glycerohyalurosomes was able to counteract the damages induced in the fibroblasts by hydrogen peroxide to a better extent (viability~110%) than that loaded in the other vesicles (viability~100%), and effectively promoted their proliferation and migration ensuring the healing of the wound performed in a cell monolayer (scratch assay) during 48 h of experiment. Overall in vitro results confirmed the potential of glycerohyalurosomes as delivery systems for T. marum extract for the treatment of skin lesions connected with oxidative stress.

Canthaxanthin Biofabrication, Loading in Green Phospholipid Vesicles and Evaluation of In Vitro Protection of Cells and Promotion of Their Monolayer Regeneration.

In the present study, canthaxanthin was produced by biofermentation from Dietzia natronolimnaea HS-1 (D. natronolimnaea) and was loaded in phospholipid vesicles prepared with natural component using an easy and low dissipative method. Indeed, glycerosomes, hyalurosomes, and glycerohyalurosomes were prepared by direct hydration of both phosphatidylcholine and the biotechnological canthaxanthin, avoiding the use of organic solvents. Vesicles were sized from 63 nm to 87 nm and highly negatively charged. They entrapped a high number of the biomolecules and were stable on storage. Canthaxanthin-loaded vesicles incubated with fibroblasts did not affect their viability, proving to be highly biocompatible and capable of inhibiting the death of fibroblasts stressed with hydrogen peroxide. They reduced the nitric oxide expression in macrophages treated with lipopolysaccharides. Moreover, they favoured the cell migration in an in vitro lesion model. Results confirmed the health-promoting potential of canthaxanthin in skin cells, which is potentiated by its suitable loading in phospholipid vesicles, thus suggesting the possible use of these natural bioformulations in both skin protection and regeneration, thanks to the potent antioxidant, anti-inflammatory and antiageing effects of canthaxanthin.

Magnolol and Honokiol: Two Natural Compounds with Similar Chemical Structure but Different Physicochemical and Stability Properties.

Magnolia spp. extracts are known for their use in traditional Korean, Chinese, and Japanese medicine in the treatment of gastrointestinal disorders, anxiety, and allergies. Among their main components with pharmacological activity, the most relevant are magnolol and honokiol, which also show antitumoral activity. The objectives of this work were to study some physicochemical properties of both substances and their stability under different conditions of temperature, pH, and oxidation. Additionally, liposomes of honokiol (the least stable compound) were formulated and characterized. Both compounds showed pH-dependent solubility, with different solubility-pH profiles. Magnolol showed a lower solubility than honokiol at acidic pH values, but a higher solubility at alkaline pH values. The partition coefficients were similar and relatively high for both compounds (log Po/w ≈ 4.5), indicating their lipophilic nature. Honokiol was less stable than magnolol, mainly at neutral and basic pH values. To improve the poor stability of honokiol, it was suitably loaded in liposomes. The obtained liposomes were small in size (175 nm), homogeneous (polydispersity index = 0.17), highly negatively charged (-11 mV), and able to incorporate high amounts of honokiol (entrapment efficiency = 93.4%). The encapsulation of honokiol in liposomes increased its stability only at alkaline pH values.

Nanotechnology for Natural Medicine: Formulation of Neem Oil Loaded Phospholipid Vesicles Modified with Argan Oil as a Strategy to Protect the Skin from Oxidative Stress and Promote Wound Healing.

Neem oil, a plant-derived product rich in bioactives, has been incorporated in liposomes and hyalurosomes modified by adding argan oil and so called argan-liposomes and argan-hyalurosomes. Argan oil has also been added to the vesicles because of its regenerative and protective effects on skin. In the light of this, vesicles were specifically tailored to protect the skin from oxidative stress and treat lesions. Argan-liposomes were the smallest vesicles (~113 nm); the addition of sodium hyaluronate led to an increase in vesicle size (~143 nm) but it significantly improved vesicle stability during storage. In vitro studies confirmed the free radical scavenging activity of formulations, irrespective of their composition. Moreover, rheological investigation confirmed the higher viscosity of argan-hyalurosomes, which avoid formulation leakage after application. In vitro studies performed by using the most representative cells of the skin (i.e., keratinocytes and fibroblasts) underlined the ability of vesicles, especially argan-liposomes and argan-hyalurosomes, to counteract oxidative stress induced in these cells by using hydrogen peroxide and to improve the proliferation and migration of cells ensuring the more rapid and even complete closure of the wound (scratch assay).

Abacavir Increases Purinergic P2X7 Receptor Activation by ATP: Does a Pro-inflammatory Synergism Underlie Its Cardiovascular Toxicity?

The cardiovascular toxicity of Abacavir is related to its purinergic structure. Purinergic P2X7-receptors (P2X7R), characterized by activation by high concentrations of ATP and with high plasticity, seem implicated. We appraise the nature of the interplay between Abacavir and P2X7R in generating vascular inflammation. The effects of Abacavir on leukocyte-endothelium interactions were compared with those of its metabolite carbovir triphosphate (CBV-TP) or ATP in the presence of apyrase (ATP-ase) or A804598 (P2X7R-antagonist). CBV-TP and ATP levels were evaluated by HPLC, while binding of Abacavir, CBV-TP and ATP to P2X7R was assessed by radioligand and docking studies. Hypersensitivity studies explored a potential allosteric action of Abacavir. Clinical concentrations of Abacavir (20 µmol/L) induced leukocyte-endothelial cell interactions by specifically activating P2X7R, but the drug did not show affinity for the P2X7R ATP-binding site (site 1). CBV-TP levels were undetectable in Abacavir-treated cells, while those of ATP were unaltered. The effects of Abacavir were Apyrase-dependent, implying dependence on endogenous ATP. Exogenous ATP induced a profile of proinflammatory actions similar to Abacavir, but was not entirely P2X7R-dependent. Docking calculations suggested ATP-binding to sites 1 and 2, and Abacavir-binding only to allosteric site 2. A combination of concentrations of Abacavir (1 µmol/L) and ATP (0.1 µmol/L) that had no effect when administered separately induced leukocyte-endothelium interactions mediated by P2X7R and involving Connexin43 channels. Therefore, Abacavir acts as a positive allosteric modulator of P2X7R, turning low concentrations of endogenous ATP themselves incapable of stimulating P2X7R into a functional proinflammatory agonist of the receptor.

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.

From waste to health: sustainable exploitation of grape pomace seed extract to manufacture antioxidant, regenerative and prebiotic nanovesicles within circular economy.

Pomace seed extract loaded vesicles were prepared as promising technological and green solution to exploit agri-food wastes and by-products, and develop high value-added products for human health. An antioxidant extract rich in bioactive compounds (epicatechins, catechin, gallic acid, quercetin and procynidins) was obtained from the seeds isolated from the pomace of Cannonau red grape cultivar. The extract was incorporated into phospholipid vesicles ad hoc formulated for intestinal delivery, by combining them, for the first time, whit a maltodextrin (Glucidex). Glucidex-transfersomes, glucidex-hyalurosomes and glucidex-hyalutransferomes were prepared, characterized and tested. Glucidex-liposomes were used as reference. All vesicles were small in size (~ 150 nm), homogeneously dispersed and negatively charged. Glucidex-transfersomes and especially glucidex-hyalutransfersomes disclosed an unexpected resistance to acidic pH and high ionic strength, as they maintained their physico-chemical properties (size and size distribution) after dilution at pH 1.2 simulating the harsh gastric conditions. Vesicles were highly biocompatible and able to counteract the oxidative damages induced in Caco-2 cells by using hydrogen peroxide. Moreover, they promoted the formation of Lactobacillus reuteri biofilm acting as prebiotic formulation. Overall results suggest the potential of glucidex-hyalutransfersomes as food supplements for the treatment of intestinal disorders.

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.

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.