Correction: Innovative snail-mucus-extract (SME)-coated nanoparticles exhibit anti-inflammatory and anti-proliferative effects for potential skin cancer prevention and treatment.

[This corrects the article DOI: 10.1039/D4RA00291A.].

Evaluation of Crocin Content and In Vitro Antioxidant and Anti-Glycation Activity of Different Saffron Extracts.

Crocin, a glycoside carotenoid that exhibits several health benefits, is mainly obtained from saffron (Crocus sativus L.), whose quality and content of phytochemicals can be strongly affected by environmental conditions. Therefore, in this work, the crocin content and in vitro antioxidant activity of saffron extracts obtained from three different varieties (Greek, Sicilian, and Iranian saffron) were assessed. Crocin content in saffron extracts was quantified via ultra-performance liquid chromatography coupled with mass spectrometry. The antioxidant activity of saffron extracts was evaluated using the oxygen radical absorbance capacity (ORAC) assay and nitric oxide (NO) radical scavenging test. The Maillard reaction was used to assess anti-glycation activity. Although the Sicilian and Iranian saffron extracts contained higher amounts of crocin (128 ± 6 ng/mL and 126 ± 4 ng/mL, respectively) compared to the Greek extracts (111 ± 2 ng/mL), ORAC values (50.9 ± 0.5) and % NO inhibition (35.2 ± 0.2) were higher for the Greek variety, which displayed a total phenolic content about two-fold greater than that of the other two extracts. Sicilian and Greek saffron had similar anti-glycation activities, while Iranian saffron was less effective. These results suggest that the antioxidant activity of saffron extracts could be ascribed to their naturally occurring complex mixture of phytochemicals, deserving further investigation as supplements to prevent pathological conditions induced by radical species.

Worldwide Research Trends on Milk Containing Only A2 ß-Casein: A Bibliometric Study.

The protein fraction of ß-casein may play a key role in the manifestation of a new intolerance: milk protein intolerance. The most common forms of ß-casein among dairy cattle breeds are A1 and A2 ß-casein. During gastrointestinal digestion of A1 ß-casein, an opioid called peptide ß-casomorphin-7 (BCM-7) is more frequently released, which can lead to adverse health outcomes. For that reason, novel products labelled as "A2 milk" or "A1-free dairy products" have appeared on the market. In this context, a bibliometric analysis on A2 ß-casein research was carried out through the Web of Science (WoS) database. The main objective of this work was to provide an overview of the state of the art in the field of ß-casein A2 by analyzing the number of publications per year, trends in thematic content, the most frequently used terms, and the most important institutions and countries in the field. This bibliometric study showed that a greater effort is needed to determine the possible implications of this novel product for human health and the market.

Impacto psicológico de la pandemia COVID-19 en cinco países de Latinoamérica / Psychological impact of the COVID-19 pandemic on five Latin American countries

Resumen Introducción: El distanciamiento social y la cuarentena han probado tener efectos negativos en la salud mental de las poblaciones, a saber: miedo, ansiedad, depresión y sintomatología de estrés postraumático. La resiliencia emerge como variable amortiguadora del impacto. El objetivo del estudio fue comparar el impacto psicológico del COVID-19 en varios países latinoamericanos. Método: se obtuvo una muestra de 1184 participantes de México, Cuba, Chile, Colombia y Guatemala; cuya edad osciló entre 18 y 83 años (M = 38.78, DT = 13.81). Se aplicó una encuesta sobre síntomas médicos asociados al COVID-19 con tres instrumentos para evaluar: (1) síntomas de depresión, ansiedad y estrés, (2) impacto del evento y (3) resiliencia. Resultados: Las personas más jóvenes, con mayor cantidad de síntomas médicos y con mayores puntajes de impacto del evento tienden a presentar mayor sintomatología depresiva, ansiosa y estrés, siendo el impacto del evento el predictor más determinante. La resiliencia fue el predictor protector contra la depresión, ansiedad y estrés. Conclusiones: Los resultados muestran las diferencias en la respuesta psicológica ante la pandemia del COVID-19 en cada país, y sugieren la necesidad del desarrollo de políticas públicas enfocadas en la prevención y la promoción de la salud integral ante emergencias sanitarias.

Abstract Introduction: Social distancing and quarantine have proven to have negative effects on the mental health of populations, namely fear, anxiety, depression and post-traumatic stress symptoms. Resilience emerges as a buffering variable for such impact. The objective of this study was to compare the psychological impact of COVID-19 in several Latin American countries. Method: A sample of 1184 participants from Mexico, Cuba, Chile, Colombia and Guatemala was obtained; whose age ranged from 18 to 83 years old (M = 38.78, SD = 13.81). A survey on medical symptoms associated with COVID-19 and three instruments to evaluate: (1) depression, anxiety and stress, (2) impact of the event and (3) resilience were administered. Results: Younger people, with more symptoms associated with COVID-19 and those who reported higher scores of impact of event tended to present greater depressive, anxious and stress symptomatology. The impact of the event was the most determinant predictor. Resilience was protective against the impact of event, depression, anxiety and stress. Conclusions: The results show the differences in the psychological response to COVID-19 in each country and suggesting the need to develop public policies focused on prevention and promotion of integral health when facing sanitary emergencies.

In Vitro Skin Permeation of Idebenone from Lipid Nanoparticles Containing Chemical Penetration Enhancers.

Lipid nanoparticles (LNPs) have been proposed as carriers for drug skin delivery and targeting. As LNPs effectiveness could be increased by the addition of chemical penetration enhancers (PE), in this work, the feasibility of incorporating PE into LNPs to improve idebenone (IDE) targeting to the skin was investigated. LNPs loading IDE 0.7% w/w were prepared using hydrophilic (propylene glycol, PG, 10% w/w or N-methylpyrrolidone, NMP, 10% w/w) and/or lipophilic PE (oleic acid, OA, 1% w/w; isopropyl myristate, IPM, 3.5% w/w; a mixture of 0.5% w/w OA and 2.5% w/w IPM). All LNPs showed small sizes (<60 nm), low polydispersity index and good stability. According to the obtained results, IDE release from LNPs was not the rate-limiting step in IDE skin penetration. No IDE permeation was observed through excised pigskin from all LNPs, while the greatest increase of IDE penetration into the different skin layers was obtained using the mixture OA/IPM. The antioxidant activity of IDE-loaded LNPs, determined by the oxygen radical absorbance capacity assay, was greater than that of free IDE. These results suggest that the use of suitable PE as LNPs components could be regarded as a promising strategy to improve drug targeting to the skin.

Precautionary Behaviors during the Second and Third Phases of the COVID-19 Pandemic: Comparative Study in the Latin American Population.

The population's behavioral responses to containment and precautionary measures during the COVID-19 pandemic have played a fundamental role in controlling the contagion. A comparative analysis of precautionary behaviors in the region was carried out. A total of 1184 people from Mexico, Colombia, Chile, Cuba, and Guatemala participated through an online survey containing a questionnaire on sociodemographic factors, precautionary behaviors, information about COVID-19, concerns, maintenance of confinement, and medical symptoms associated with COVID-19. Cubans reported the highest scores for information about COVID-19. Colombians reported less frequent usage of precautionary measures (e.g., use of masks), but greater adherence to confinement recommendations in general, in contrast to the low levels of these behaviors in Guatemalans. Chileans reported greater pandemic-related concerns and the highest number of medical symptoms associated with COVID-19. These findings allow a partial characterization of the Latin American population's responses during the second and third phases of the COVID-19 pandemic and highlight the importance of designing and managing public health policies according to the circumstances of each population when facing pandemics.

Neuroprotective effects of Rosmarinus officinalis L. extract in oxygen glucose deprivation (OGD)-injured human neural-like cells.

Rosmarinus officinalis L. (RO), an aromatic plant used as food condiment and in traditional medicine, exerts numerous beneficial properties including antioxidant, analgesic and neuroprotective effects. Onset and progression of homeostatic imbalances observed in the early phases of a number of neurodegenerative diseases, have been associated with a gap junction (GJ)-dependent increased membrane permeability and alterations of connexins (Cxs), including Cx43. Here, we evaluate spray-dried RO extract (SDROE)-mediated effects on cell viability, apoptosis and Cx43-based intercellular communication using human SH-SY5Y neuron-like and human A-172 glial-like cells in an in vitro model of oxygen glucose deprivation (OGD) injury. We found that SDROE exerts a protective action in OGD-injured cells, increasing cell viability and metabolic turnover and decreasing Cx43-based cell coupling. These data suggest that SDROE-mediated Cx43 reduction may be the molecular basis for its beneficial effects to be exploited for preventive treatment against the risk of some neurodegenerative disorders.

Green biotechnology for valorisation of residual biomasses in nutraceutic sector: Characterization and extraction of bioactive compounds from grape pomace and evaluation of the protective effects in vitro.

The grape pomace (GP) is an important by-product of winemaking, accounting for about 13-25% of the grapes processed. The aim of this work was to investigate the nutritional and antioxidant composition of GP obtained from Nero d'Avola (NA) grape, one of the most important indigenous varieties in Italy, in order to verify application in nutraceutics. Seeds and skin of the GP were studied for their nutritional and antioxidants composition, fatty acid and polyphenols profile, bioactives properties in vitro, by gravimetric, spectrophotometric and chromatographic techniques. The results showed that NAGP seeds are rich in the beneficial polyunsaturated fatty acids and that the polyphenols extracted from the GP skin present a strong antiradical and antiproliferative activity, attested also in vitro, in human skin fibroblast (HS-68) and in hepatoma cell line (Hep-G2). Obtained results underline the possibility to employ this residual biomass for nutraceuticals application, contributing also to increase the sustainability.

In Vitro Antioxidant and Anti-Glycation Activity of Resveratrol and Its Novel Triester with Trolox.

Resveratrol (RSV) is well known for its many beneficial activities, but its unfavorable physicochemical properties impair its effectiveness after systemic and topical administration; thus, several strategies have been investigated to improve RSV efficacy. With this aim, in this work, we synthesized a novel RSV triester with trolox, an analogue of vitamin E with strong antioxidant activity. The new RSV derivative (RSVTR) was assayed in vitro to evaluate its antioxidant and anti-glycation activity compared to RSV. RSVTR chemical stability was assessed at pH 2.0, 6.8, and 7.2 and different storage temperatures (5 °C, 22 °C, and 37 °C). An influence of pH stronger than that of temperature on RSVTR half-life values was pointed out, and RSVTR greatest stability was observed at pH 7.2 and 5 °C. RSVTR showed a lower antioxidant ability compared to RSV (determined by the oxygen radical absorbance capacity assay) while its anti-glycation activity (evaluated using the Maillard reaction) was significantly greater than that of RSV. The improved ability to inhibit the glycation process was attributed to a better interaction of RSVTR with albumin owing to its increased topological polar surface area value and H-bond acceptor number compared to RSV. Therefore, RSVTR could be regarded as a promising anti-glycation agent worthy of further investigations.

Strategies to Improve Resveratrol Systemic and Topical Bioavailability: An Update.

In recent years, a great deal of attention has been paid to natural compounds due to their many biological effects. Polyphenols are a class of plant derivatives that have been widely investigated for preventing and treating many oxidative stress-related pathological conditions, such as neurodegenerative and cardiovascular diseases, cancer, diabetes mellitus and inflammation. Among these polyphenols, resveratrol (RSV) has attracted considerable interest owing to its high antioxidant and free radical scavenging activities. However, the poor water solubility and rapid metabolism of RSV lead to low bioavailability, thus limiting its clinical efficacy. After discussing the main biochemical mechanisms involved in RSV biological activities, this review will focus on the strategies attempted to improve RSV effectiveness, both for systemic and for topical administration. In particular, technological approaches involving RSV incorporation into different delivery systems such as liposomes, polymeric and lipid nanoparticles, microemulsions and cyclodextrins will be illustrated, highlighting their potential clinical applications. In addition, chemical modifications of this antioxidant aimed at improving its physicochemical properties will be described along with the results of in vitro and in vivo studies.

(2S)-N-2-methoxy-2-phenylethyl-6,7-benzomorphan compound (2S-LP2): Discovery of a biased mu/delta opioid receptor agonist.

The pivotal role of the stereocenter at the N-substituent of the 6,7-benzomorphan scaffold was investigated combining synthetic and pharmacological approaches. 2R- and 2S-diastereoisomers of the multitarget MOR/DOR antinociceptive ligand LP2 (1) were synthesized and their pharmacological profile was evaluated in in vitro and vivo assays. From our results, 2S-LP2 (5) showed an improved pharmacological profile in comparison to LP2 (1) and 2R-LP2 (4). 2S-LP2 (5) elicited an antinociceptive effect with a 1.5- and 3-times higher potency than LP2 (1) and R-antipode (4), respectively. In vivo effect of 2S-LP2 (5) was consistent with the improved MOR/DOR efficacy profile assessed by radioligand binding assay, to evaluate the opioid receptor affinity, and BRET assay, to evaluate the capability to promote receptor/G-protein and receptor/ß-arrestin 2 interaction. 2S-LP2 (5) was able to activate, with different efficacy, G-protein pathway over ß-arrestin 2, behaving as biased agonist at MOR and mainly at DOR. Considering the therapeutic potential of both multitarget MOR/DOR agonism and functional selectivity over G-protein, the 2S-LP2 (5) biased multitarget MOR/DOR agonist could provide a safer treatment opportunity.

Simultaneous targeting of MOR/DOR: A useful strategy for inflammatory pain modulation.

Development of new analgesics endowed with mu/delta opioid receptor (MOR/DOR) activity represents a promising alternative to MOR selective compounds because of their better therapeutic and tolerability profile. Lately, we have synthetized the MOR/DOR agonist LP2 that showed a long lasting antinociceptive activity in the tail flick test, an acute pain model. Here, we investigate whether LP2 is also effective in the mouse formalin test, a model of inflammatory pain sustained by mechanisms of central sensitization. Moreover, we evaluated a possible peripheral component of LP2 analgesic activity. Different doses of LP2 were tested after either intraperitoneal (i.p.) or intraplantar (i.pl.) administration. LP2 (0.75-1.00 mg/kg, i.p.), dose-dependently, counteracted both phases of the formalin test after i.p. administration. The analgesic activity of LP2 (0.75-1.00 mg/kg) was completely blocked by a pretreatment with the opioid antagonist naloxone (3 mg/kg, i.p.). Differently, the pretreatment with naloxone methiodide (5 mg/kg, i.p.), a peripherally restricted opioid antagonist, completely blocked the lower analgesic dose of LP2 (0.75 mg/kg) but only partially relieved the antinociceptive effects of LP2 at the dose of 1.00 mg/kg, thus revealing a peripheral analgesic component of LP2. I.pl. injections of LP2 (10-20 µg/10 µl) were also performed to investigate a possible effect of LP2 on peripheral nerve terminals. Nociceptive sensitization, which occur both at peripheral and central level, is a fundamental step for pain chronicization, thus LP2 is a promising drug for pain conditions characterized by nociceptive sensitization.

Differential Scanning Calorimetry Analyses of Idebenone-Loaded Solid Lipid Nanoparticles Interactions with a Model of Bio-Membrane: A Comparison with In Vitro Skin Permeation Data.

Differential scanning calorimetry (DSC) has emerged as a helpful technique both to characterize drug delivery systems and to study their interactions with bio-membranes. In this work, we compared idebenone (IDE)-loaded solid lipid nanoparticle (SLN) interactions with bio-membranes assessed by DSC with previous in vitro skin penetration data to evaluate the feasibility of predicting IDE skin penetration using DSC analyses. In vitro interactions experiments were performed using multi-lamellar liposomes as a model of bio-membrane. Enthalpy changes (ΔH) and transition temperature (Tm) were assessed during nine repeated DSC scans to evaluate IDE-loaded SLN⁻bio-membrane interactions over time. Analyzing ΔH and Tm values for each scan, we observed that the difference of ΔH and Tm values between the first and the last scan seemed to be related to SLN ability to locate IDE in the epidermis and in the stratum corneum, respectively. Therefore, the results of this study suggest the possibility of qualitatively predicting in vitro IDE skin penetration from IDE-loaded SLN utilizing the calorimetric parameters obtained from interaction experiments between the carriers under investigation and a model of bio-membrane.

Benzomorphan skeleton, a versatile scaffold for different targets: A comprehensive review.

Despite the fact that the benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets. Collectively, the SARs data have highlighted that the benzomorphan nucleus could be regarded as a useful template for the synthesis of drug candidates for different targets.

Synthesis and Structure-Activity Relationships of (-)-cis-N-Normetazocine-Based LP1 Derivatives.

(−)-cis-N-Normetazocine represents a rigid scaffold able to mimic the tyramine moiety of endogenous opioid peptides, and the introduction of different N-substituents influences affinity and efficacy of respective ligands at MOR (mu opioid receptor), DOR (delta opioid receptor), and KOR (kappa opioid receptor). We have previously identified LP1, a MOR/DOR multitarget opioid ligand, with an N-phenylpropanamido substituent linked to (−)-cis-N-Normetazocine scaffold. Herein, we report the synthesis, competition binding and calcium mobilization assays of new compounds 10⁻16 that differ from LP1 by the nature of the N-substituent. In radioligand binding experiments, the compounds 10⁻13, featured by an electron-withdrawing or electron-donating group in the para position of phenyl ring, displayed improved affinity for KOR (Ki = 0.85⁻4.80 μM) in comparison to LP1 (7.5 μM). On the contrary, their MOR and DOR affinities were worse (Ki = 0.18⁻0.28 μM and Ki = 0.38⁻1.10 μM, respectively) with respect to LP1 values (Ki = 0.049 and 0.033 μM). Analogous trends was recorded for the compounds 14⁻16, featured by indoline, tetrahydroquinoline, and diphenylamine functionalities in the N-substituent. In calcium mobilization assays, the compound 10 with a p-fluorophenyl in the N-substituent shared the functional profile of LP1 (pEC50MOR = 7.01), although it was less active. Moreover, the p-methyl- (11) and p-cyano- (12) substituted compounds resulted in MOR partial agonists and DOR/KOR antagonists. By contrast, the derivatives 13⁻15 resulted as MOR antagonists, and the derivative 16 as a MOR/KOR antagonist (pKBMOR = 6.12 and pKBKOR = 6.11). Collectively, these data corroborated the critical role of the N-substituent in (−)-cis-N-Normetazocine scaffold. Thus, the new synthesized compounds could represent a template to achieve a specific agonist, antagonist, or mixed agonist/antagonist functional profile.

In Vitro Evaluation of Sunscreen Safety: Effects of the Vehicle and Repeated Applications on Skin Permeation from Topical Formulations.

The evaluation of UV-filter in vitro percutaneous absorption allows the estimation of the systemic exposure dose (SED) and the margin of safety (MoS) of sunscreen products. As both the vehicle and pattern of application may affect sunscreen safety and efficacy, we evaluated in vitro release and skin permeation of two widely used UV-filters, octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM) from topical formulations with different features (oil in water (O/W) emulsions with different viscosity, water in oil (W/O) emulsion, oils with different lipophilicity). To mimic in-use conditions, we carried out experiments repeating sunscreen application on the skin surface for three consecutive days. BMBM release from all these vehicles was very low, thus leading to poor skin permeation. The vehicle composition significantly affected OMC release and skin permeation, and slight increases of OMC permeation were observed after repeated applications. From skin permeation data, SED and MoS values of BMBM and OMC were calculated for all the investigated formulations after a single application and repeated applications. While MoS values of BMBM were always well beyond the accepted safety limit, the safety of sunscreen formulations containing OMC may depend on the vehicle composition and the application pattern.

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy.

The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. Unfortunately, IDE's unfavorable physicochemical properties such as poor water solubility and high lipophilicity impair its bioavailability after oral and topical administration and prevent its parenteral use. In recent decades, many strategies have been proposed to improve IDE effectiveness in the treatment of neurodegenerative diseases and skin disorders. After a brief description of IDE potential therapeutic applications and its pharmacokinetic and pharmacodynamic profile, this review will focus on the different approaches investigated to overcome IDE drawbacks, such as IDE incorporation into different types of delivery systems (liposomes, cyclodextrins, microemulsions, self-micro-emulsifying drug delivery systems, lipid-based nanoparticles, polymeric nanoparticles) and IDE chemical modification. The results of these studies will be illustrated with emphasis on the most innovative strategies and their future perspectives.

Solid Lipid Nanoparticles Loading Idebenone Ester with Pyroglutamic Acid: In Vitro Antioxidant Activity and In Vivo Topical Efficacy.

Idebenone (IDE), a strong antioxidant widely investigated for the treatment of neurodegenerative diseases and skin disorders, shows low oral and topical bioavailability due to its unfavorable physico-chemical properties. In this work, to improve IDE topical effectiveness, we explored a two-steps approach: (1) we synthesized an IDE ester (IDEPCA) with pyroglutamic acid, a molecule whose hydrating effects are well known; (2) we loaded IDEPCA into solid lipid nanocarriers (SLN). We evaluated in vitro antioxidant and anti-glycation activity and in vivo hydrating effects after topical application in human volunteers from gel vehicles of IDEPCA SLN in comparison to IDE SLN. All SLN showed good technological properties (mean particle size < 25 nm, polydispersity index < 0.300, good stability). The oxygen radical absorbance capacity assay showed that IDEPCA SLN and IDE SLN had similar antioxidant activity while IDEPCA SLN were more effective in the in vitro NO scavenging assay. Both IDEPCA and IDE SLN showed the same effectiveness in inhibiting the formation of advanced glycation end products. In vivo experiments pointed out a better hydrating effect of IDEPCA SLN in comparison to IDE SLN. These results suggest that the investigated approach could be a promising strategy to obtain topical formulations with increased hydrating effects.

Resveratrol-Loaded Lipid Nanocarriers: Correlation between In Vitro Occlusion Factor and In Vivo Skin Hydrating Effect.

Lipid nanocarriers show occlusive properties that may be related to their ability to improve skin hydration. The aim of this work was to evaluate the relationship between in vitro occlusion factor and in vivo skin hydration for three types of lipid nanocarriers: nanoemulsions (NEs), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These lipid nanocarriers were loaded with trans-resveratrol (RSV) and incorporated in gel vehicles. In vitro occlusion factor was in the order SLNs > NLCs > NEs. Gels containing unloaded or RSV loaded lipid nanocarriers were applied on the back of a hand of 12 healthy volunteers twice a day for one week, recording skin hydration changes using the instrument Soft Plus. An increase of skin hydration was observed for all lipid nanocarriers (SLNs > NLCs > NEs). RSV loading into these nanocarriers did not affect in vitro and in vivo lipid nanocarriers effects. A linear relationship (r² = 0.969) was observed between occlusion factor and in vivo increase of skin hydration. Therefore, the results of this study showed the feasibility of using the occlusion factor to predict in vivo skin hydration resulting from topical application of different lipid nanocarriers loading an active ingredient with no inherent hydrating activity.

Rosemary Essential Oil-Loaded Lipid Nanoparticles: In Vivo Topical Activity from Gel Vehicles.

Although rosemary essential oil (EO) shows many biological activities, its topical benefits have not been clearly demonstrated. In this work, we assessed the effects on skin hydration and elasticity of rosemary EO after topical application via gel vehicles in human volunteers. To improve its topical efficacy, rosemary EO was loaded into lipid nanoparticles (NLCs) consisting of cetyl palmitate as a solid lipid, and non-ionic surfactants. Such NLCs were prepared using different ratios of EO/solid lipid and those containing EO 3% w/w and cetyl pamitate 7% w/w were selected for in vivo studies, showing the best technological properties (small particle size, low polydispersity index and good stability). Gels containing free EO or EO-loaded NLCs were applied on the hand skin surface of ten healthy volunteers twice a day for one week. Skin hydration and elasticity changes were recorded using the instrument Soft Plus. Gels containing EO-loaded NLCs showed a significant increase in skin hydration in comparison with gels containing free EO. Skin elasticity increased, as well, although to a lesser extent. The results of this study point out the usefulness of rosemary EO-loaded NLCs for the treatment of cutaneous alterations involving loss of skin hydration and elasticity.