Influence of Clinical and Psychosocial Factors on the Adherence to Topical Treatment in Psoriasis.

(1) Background: Psoriasis is a common chronic inflammatory skin disease with different manifestations, affecting the quality of life at social, emotional, and professional dimensions and requiring long-term treatment. This study aimed to investigate the effect of psychosocial and clinical factors on adherence to topical treatment in psoriasis. (2) Methods: Self-reported measures and weighing the medicines were used to assess adherence. Psychopathological symptoms were measured using the Brief Symptoms Inventory (BSI). Social and clinical factors were assessed by a sociodemographic and clinical questionnaire. Adherence to treatment with topical medication was assessed using a sample of 102 psoriasis patients. (3) Results: The explanatory models of adherence to topical treatment in psoriasis translated into positive associations between adherence and the education level (higher education) (p = 0.03; φ = 0.23), the single-family household (p = 0.01; φ = 0.44), active employment status (p = 0.05; φ = -0.19), familiar history of psoriasis (p = 0.04; φ = -0.21), and the presence of obsessive-compulsive symptoms (p = 0.01; d = 0.29). (4) Conclusions: In patients who present the characteristics identified that influence non-adherence, instructions should be reinforced to increase adherence. The experimental mortality (39.6%) reduced the sample size, representing a limitation of the study.

Current Insights on Lipid-Based Nanosystems 2023.

Among the different types of nanosystems that have been investigated for therapeutic use, lipid-based ones are the most explored, as they have advantages over non-lipid nanosystems, especially for improving the transport and efficacy of drugs through different routes of administration, such as ocular, cutaneous, intranasal, and intravenous [...].

In situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nose-to-brain delivery: development, characterization and deposition studies in a 3D-printed human nasal cavity model.

The nasal route has been investigated as a promising alternative for drug delivery to the central nervous system, avoiding passage through the blood-brain barrier and improving bioavailability. In this sense, it is necessary to develop and test the effectiveness of new formulations proposed for the management of neurological disorders. Thereby, the aim of this work was to develop and characterize an ion sensitive in situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nasal delivery in the treatment of epilepsy. Physical characterization of the developed formulations was performed and included the evaluation of rheological features, particle size, polydispersity index (PDI) and zeta potential (ZP) of an in situ hydrogel containing DZP-NLC. Afterwards, in vitro drug release, in vitro mucoadhesion and biocompatibility studies with RPMI 2650 nasal cells were performed. The in situ hydrogel containing DZP-NLC was aerosolized with a nasal spray device specifically designed for nose-to-brain delivery (VP7 multidose spray pump with a 232 N2B actuator) and characterized for droplet size distribution and spray cone angle. Finally, the deposition pattern of this hydrogel was evaluated in a 3D-printed human nasal cavity model. The developed in situ hydrogel containing DZP-NLC presented adequate characteristics for nasal administration, including good gelling ability, mucoadhesiveness and prolonged drug release. In addition, after inclusion in the hydrogel net, the particle size (81.79 ± 0.53 nm), PDI (0.21 ± 0.10) and ZP (-30.90 ± 0.10 mV), of the DZP-NLC remained appropriate for nose-to-brain delivery. Upon aerosolization in a nasal spray device, a suitable spray cone angle (22.5 ± 0.2°) and adequate droplet size distribution (Dv (90) of 317.77 ± 44.12 µm) were observed. Biocompatibility studies have shown that the developed formulation is safe towards RPMI 2650 cells in concentrations up to 100 µg/mL. Deposition studies on a 3D-printed human nasal cavity model revealed that the best nasal deposition profile was obtained upon formulation administration without airflow and at an angle from horizontal plane of 75°, resulting in 47% of administered dose deposited in the olfactory region and 89% recovery. The results of this study suggested that the intranasal administration of the developed in situ hydrogel containing DZP-NLC could be a promising alternative to the conventional treatments for epilepsy.

Intranasal Lipid Nanoparticles Containing Bioactive Compounds Obtained from Marine Sources to Manage Neurodegenerative Diseases.

Marine sources contain several bioactive compounds with high therapeutic potential, such as remarkable antioxidant activity that can reduce oxidative stress related to the pathogenesis of neurodegenerative diseases. Indeed, there has been a growing interest in these natural sources, especially those resulting from the processing of marine organisms (i.e., marine bio-waste), to obtain natural antioxidants as an alternative to synthetic antioxidants in a sustainable approach to promote circularity by recovering and creating value from these bio-wastes. However, despite their expected potential to prevent, delay, or treat neurodegenerative diseases, antioxidant compounds may have difficulty reaching the brain due to the need to cross the blood-brain barrier (BBB). In this regard, alternative delivery systems administered by different routes have been proposed, including intranasal administration of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which have shown promising results. Intranasal administration shows several advantages, including the fact that molecules do not need to cross the BBB to reach the central nervous system (CNS), as they can be transported directly from the nasal cavity to the brain (i.e., nose-to-brain transport). The benefits of using SLN and NLC for intranasal delivery of natural bioactive compounds for the treatment of neurodegenerative diseases have shown relevant outcomes through in vitro and in vivo studies. Noteworthy, for bioactive compounds obtained from marine bio-waste, few studies have been reported, showing the open potential of this research area. This review updates the state of the art of using SLN and NLC to transport bioactive compounds from different sources, in particular, those obtained from marine bio-waste, and their potential application in the treatment of neurodegenerative diseases.

An In Vitro Evaluation of the Potential Neuroprotective Effects of Intranasal Lipid Nanoparticles Containing Astaxanthin Obtained from Different Sources: Comparative Studies.

The intranasal route has been suggested as a promising alternative to improve the direct transport of molecules to the brain, avoiding the need to cross the blood-brain barrier (BBB). In this area, the use of lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has been highlighted as a promising strategy to improve the treatment of neurodegenerative diseases. In this work, formulations containing SLN and NLC that were loaded with astaxanthin that was obtained from different sources (astaxanthin extract (AE) from the algae Haematococcus pluvialis and pure astaxanthin (PA) from the fungi Blakeslea trispora) were prepared for nose-to-brain administration, and comparative in vitro experiments were performed to evaluate the biocompatibility of the formulations with nasal (RPMI 2650) and neuronal (SH-SY5Y) cells. Afterwards, the antioxidant activity of the formulations was evaluated for its potential neuroprotective effects, using different chemical aggressors. Finally, the cellular uptake of the astaxanthin was evaluated for the formulations that showed the greatest neuroprotection of the neuronal cells against chemical-induced damage. On the production day, all the formulations showed a particle size, a high encapsulation efficiency (EE), the presence of nanoparticles with a typical spherical shape, and a polydispersity index (PDI) and zeta potential (ZP) that are suitable for nose-to-brain administration. After three months of storage at room temperature, no significant changes were observed in the characterization parameters, predicting a good long-term stability. Furthermore, these formulations were shown to be safe with concentrations of up to 100 µg/mL in differentiated SH-SY5Y and RPMI 2650 cells. Regarding neuroprotection studies, the PA-loaded SLN and NLC formulations showed an ability to counteract some mechanisms of neurodegeneration, including oxidative stress. Moreover, when compared with the PA-loaded SLN, the PA-loaded NLC showed greater neuroprotective effects against the cytotoxicity induced by aggressors. In contrast, the AE-loaded SLN and NLC formulations showed no significant neuroprotective effects. Although further studies are needed to confirm these neuroprotective effects, the results of this study suggest that the intranasal administration of PA-loaded NLC may be a promising alternative to improve the treatment of neurodegenerative diseases.

Benefits of skin application of piceatannol-A minireview.

The skin is the largest organ of the human body and has several functions such as barrier against external agents, the maintenance of temperature and homeostatic functions. Skin ageing is a natural process that can be influenced by environmental factors, intrinsic skin factors and lifestyle. UV light plays an important role in skin ageing and can cause spots, requiring the use of depigmenting agents. Nowadays, there is a great demand for ingredients that prevent skin ageing, with natural agents occupying a promising position. Among the natural agents, polyphenols, such as resveratrol and piceatannol, found in grapes, passion fruits and other fruits, have a huge relevance. Great benefits of piceatannol have been reported, so thus, this work focuses specifically on a review of the literature regarding the application of this polyphenol in skin care products. This polyphenol can be used in a wound-healing, or as anti-ageing, antioxidant, anti-acne and skin whitening, among other effects.

Up-to-Date Overview of the Use of Natural Ingredients in Sunscreens.

The photoprotective skincare segment is in high demand to meet consumer concerns on UV-induced skin damage, with a recent trend towards sunscreen alternatives with a natural origin. In this study, the use of natural ingredients, either from terrestrial or marine origin, in a panel of 444 sunscreen commercial formulations (2021) was analyzed. Ingredients from terrestrial organisms represent the large majority found in the analyzed sunscreen formulations (48%), whereas marine ingredients are present only in 13% of the analyzed products. A deeper analysis regarding the most prevalent families of ingredients from terrestrial and marine organisms used as top ingredients is also presented, as well as their mechanisms of action. This study provides an up-to-date overview of the sunscreen market regarding the use of natural ingredients, which is of relevance for scientists involved in the development of new sunscreens to identify opportunities for innovation.

A review of the continuous professional development system for pharmacists.

BACKGROUND: The Portuguese Pharmaceutical Society (PPS) implemented a system of Continuous Professional Development (CPD) for pharmacists in 2004. This system has evolved throughout the years, and currently all active pharmacists in Portugal are required to participate in the CPD program. Each CPD cycle takes 5 years. In each cycle, pharmacists must collect 15 CPD points, through participation in educational activities. The PPS accreditation process is managed via an online platform, where education/training providers, as well as pharmacists themselves, can submit educational activities for accreditation. Pharmacists may access their CPD status and assess their development at any point. The objective of this study was to analyze and review the educational activities submitted by providers over a 11-year period (2009-2019). METHODS: Data from activities were retrieved from the PPS CPD online platform. All educational activities were labeled according to the area of pharmaceutical professional focus, type of promoter, and activity type. RESULTS: During the study 3685 activities were analyzed. Over the last decade, submitted activities for accreditation increased in 52.6%. A significantly high proportion (98.9%) of these activities has been accredited. Promoters of activities were mostly pharmacies sectoral associations (29.6%), consultancy/training companies (19.6%), the PPS (18.5%), pharmaceutical industry (17.7%) and wholesalers' consortia (9.0%). Academia represented only 2.3% of the total amount of educational activities. The most frequent topics were related to "pharmacology & pharmacotherapy" (9.9%), followed by "counselling" (9.8%) and "management & administration" (7.2%). The most accredited type of activities was face-to-face (68.9%) and e-learning trainings (13.1%). CONCLUSIONS: This study shows increasing interest in submitting CPD activities for accreditation between 2009 and 2019, but it also demonstrates that Academia could play a more interventive role in the lifelong learning education of Portuguese pharmacists.

Sensitive skin: Active ingredients on the spotlight.

OBJECTIVE: Sensitive skin is characterized by self-reported sensory perceptions in response to stimuli that should not provoke unpleasant sensations. Cosmetic products for sensitive skin are designed to minimize these symptoms. This study aimed to unveil the most used active ingredients for sensitive skin in facial care products from the pharmacy and parapharmacy channel. METHODS: A pool of products from the pharmacy and parapharmacy channel whose label included the expressions 'sensitive skin', 'reactive skin' or 'intolerant skin' were analysed. The active ingredients were identified from product compositions and ranked in descending order of occurrence. The scientific evidence regarding the mechanism of action and efficacy of each ingredient was also compiled. RESULTS: Eighty-eight products from 19 multinational brands were included. Niacinamide leads the top, followed by Avena sativa, allantoin, glycyrrhetinic acid and derivatives and Laminaria ochroleuca. Ingredients that can reduce skin inflammation and act on the skin barrier were used in more than half of the products analysed. The clinical studies regarding the active ingredients used in these products remain sparse and lack methodological quality. Among the top ingredients, niacinamide, panthenol and acetyl dipeptide-1 cetyl ester were the only ones studied on volunteers having sensitive skin, while acetyl dipeptide-1 cetyl ester and palmitoyl tripeptide-8 were designed to act on the molecular targets involved in this condition. CONCLUSION: This study reveals the most used active ingredients in cosmetic products for sensitive skin, as well as the scientific evidence supporting their efficacy and the mechanisms of action. This insight is meaningful for dermatologists and other health professionals to provide customized advice based on the symptomatology of individuals with sensitive skin, and for the formulation of cosmetic products and design of new active ingredients.

OBJECTIF: La peau sensible se caractérise par des perceptions sensorielles autorapportées en réponse à des stimuli qui ne devraient pas provoquer de sensations désagréables. Les produits cosmétiques pour peaux sensibles sont conçus pour minimiser ces symptômes. Cette étude visait à dévoiler les principes actifs les plus utilisés pour les peaux sensibles dans les produits de soins du visage de la pharmacie et de la chaîne de parapharmacie. MÉTHODES: Un ensemble de produits de la chaîne pharmacie et parapharmacie, dont l'étiquette comportait les expressions « peau sensible ¼, « peau réactive ¼ ou « peau intolérante ¼ ont été analysés. Les principes actifs ont été identifiés à partir des compositions du produit et classés par ordre décroissant d'occurrence. Les preuves scientifiques concernant le mécanisme d'action et l'efficacité de chaque ingrédient ont également été compilées. RÉSULTATS: Quatre-vingt-huit produits provenant de 19 marques multinationales ont été inclus. Le niacinamide est en tête, suivi de l'Avena sativa, de l'allantoïne, de l'acide glycyrrhétinique et de ses dérivés et de Laminaria ochroleuca. Des ingrédients pouvant réduire l'inflammation cutanée et agir sur la barrière cutanée ont été utilisés dans plus de la moitié des produits analysés. Les études cliniques concernant les principes actifs utilisés dans ces produits restent rares et manquent de qualité méthodologique. Parmi les principaux ingrédients, le niacinamide, le panthénol et l'ester de dipeptide acétyl-1 ont été les seuls étudiés sur des volontaires ayant une peau sensible, tandis que l'ester de dipeptide acétyl-1 et le tripeptide palmitoyl-8 ont été conçus pour agir sur les cibles moléculaires qui interviennent dans cette affection. CONCLUSION: Cette étude révèle les principes actifs les plus utilisés dans les produits cosmétiques pour les peaux sensibles, ainsi que les preuves scientifiques étayant leur efficacité et les mécanismes d'action. Cet éclairage est important pour les dermatologues et autres professionnels de la santé pour apporter des conseils personnalisés basés sur la symptomatologie des personnes ayant la peau sensible, et pour la formulation de produits cosmétiques et la conception de nouveaux principes actifs.

Does the Vehicle Matter? Real-World Evidence on Adherence to Topical Treatment in Psoriasis.

The influence of the vehicle in topical treatment adherence remains to be elucidated. The aim of this study is to analyze the influence of the pharmaceutical dosage form on adherence to topical treatment in psoriasis patients, taking into consideration the mechanical features. The adherence was evaluated in a sample of 102 psoriasis patients, followed for approximately 45 days. Adherence was calculated with a new combined methodology using a log and medication weights. The effect of the group formulation was evaluated using logistic regression models. A complex effect of the vehicle on adherence was found, mediated by the affected area. The adherence was significantly higher for patients applying gels and creams than for those using ointments, whenever the body area affected was extensive. The opposite was found when the affected area was small. Mechanical properties can partially explain the findings since gels and creams may be easier to apply. Patient beliefs and preferences regarding vehicles and their sensory attributes might also explain the results. It is noteworthy that adherence was strikingly low, with more than 75% non-adherent patients. This real-world evidence provides an insight for pharmaceutical industries and guidance for treatment prescription by physicians aiming to address the public health emergency of treatment non-adherence.

Usage of Synthetic Peptides in Cosmetics for Sensitive Skin.

Sensitive skin is characterized by symptoms of discomfort when exposed to environmental factors. Peptides are used in cosmetics for sensitive skin and stand out as active ingredients for their ability to interact with skin cells by multiple mechanisms, high potency at low dosage and the ability to penetrate the stratum corneum. This study aimed to analyze the composition of 88 facial cosmetics for sensitive skin from multinational brands regarding usage of peptides, reviewing their synthetic pathways and the scientific evidence that supports their efficacy. Peptides were found in 17% of the products analyzed, namely: acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, acetyl tetrapeptide-15, palmitoyl tripeptide-5, acetyl hexapeptide-49, palmitoyl tetrapeptide-7 and palmitoyl oligopeptide. Three out of seven peptides have a neurotransmitter-inhibiting mechanism of action, while another three are signal peptides. Only five peptides present evidence supporting their use in sensitive skin, with only one clinical study including volunteers having this condition. Noteworthy, the available data is mostly found in patents and supplier brochures, and not in randomized placebo-controlled studies. Peptides are useful active ingredients in cosmetics for sensitive skin. Knowing their efficacy and synthetic pathways provides meaningful insight for the development of new and more effective ingredients.

In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN).

The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood-brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research.

Trends in the Use of Botanicals in Anti-Aging Cosmetics.

Botanical ingredients have been used for thousands of years in skincare for their convenience as well as the diversity and abundance in compounds with biological activity. Among these, polyphenols and especially flavonoids have gained increasing prominence due to their antioxidant and anti-inflammatory properties. In this study, the most used botanical preparations in anti-aging products marketed in 2011 were determined. The analysis was repeated in 2018 for new and reformulated products. The scientific evidence for their application as active ingredients in anti-aging cosmetics and their flavonoid content was also compiled by searching in online scientific databases. Overall, in 2018, there was a noticeable increase in the use of botanical preparations in anti-aging cosmetics. However, the top three botanical species in both years were Vitis vinifera, Butyrospermum parkii, and Glycine soja, which is consistent with the greater amount of scientific evidence supporting their efficacy. Regarding the function of botanical preparations, there is a clear preference for DNA-protecting ingredients. The most prevalent flavonoids were flavan-3-ols, proanthocyanidins, and anthocyanins. This study provided an updated overview of the market trends regarding the use of botanicals in anti-aging products and documented the state of the art of scientific evidence for the most used plants.

Improving Drug Delivery for Alzheimer's Disease Through Nose-to-Brain Delivery Using Nanoemulsions, Nanostructured Lipid Carriers (NLC) and in situ Hydrogels.

Current treatments for Alzheimer's disease (AD) attenuate the progression of symptoms and aim to improve the patient's quality of life. Licensed medicines are mostly for oral administration and are limited by the difficulty in crossing the blood-brain barrier (BBB). Here in, the nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. To optimize nose-to-brain delivery, formulations of lipid-based nanosystems, namely nanoemulsions and nanostructured lipid carriers (NLC), formulated in situ gelling hydrogels have been proposed as approaches for nose-to-brain delivery. These formulations possess characteristics that facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits. It has been recommended that the manufacture of these drug delivery systems follows the quality by design (QbD) approach based on nasal administration requirements. This review provides an insight into the current knowledge of the AD, highlighting the need for an effective drug delivery to the brain. Considering the mounting interest in the use of nanoemulsions and NLC for nose-to-brain delivery, a description of drug transport pathways in the nasal cavity and the application of these nanosystems and their in situ hydrogels through the intranasal route are presented. Relevant preclinical studies are summarised, and the future prospects for the use of lipid-based nanosystems in the treatment of AD are emphasized.

Preclinical Evaluation of Lipid-Based Nanosystems.

The use of lipid-based nanosystems, including lipid nanoparticles (solid lipid nanoparticles-SLN, and nanostructured lipid carriers-NLC), nanoemulsions, and liposomes, among others, is widespread [...].

Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of in vivo studies.

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years.

In Vitro Evaluation of the Photoreactivity and Phototoxicity of Natural Polyphenol Antioxidants.

Polyphenols are a large family of natural compounds widely used in cosmetic products due to their antioxidant and anti-inflammatory beneficial properties and their ability to prevent UV radiation-induced oxidative stress. Since these compounds present chromophores and are applied directly to the skin, they can react with sunlight and exert phototoxic effects. The available scientific information on the phototoxic potential of these natural compounds is scarce, and thus the aim of this study was to evaluate the photoreactivity and phototoxicity of five phenolic antioxidants with documented use in cosmetic products. A standard ROS assay was validated and applied to screen the photoreactivity of the natural phenolic antioxidants caffeic acid, ferulic acid, p-coumaric acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and rutin. The phototoxicity potential was determined by using a human keratinocyte cell line (HaCaT), based on the 3T3 Neutral Red Uptake phototoxicity test. Although all studied phenolic antioxidants absorbed UV/Vis radiation in the range of 290 to 700 nm, only DOPAC was able to generate singlet oxygen. The generation of reactive oxygen species is an early-stage chemical reaction as part of the phototoxicity mechanism. Yet, none of the studied compounds decreased the viability of keratinocytes after irradiation, leading to the conclusion that they do not have phototoxic potential. The data obtained with this work suggests that these compounds are safe when incorporated in cosmetic products.

Double Optimization of Rivastigmine-Loaded Nanostructured Lipid Carriers (NLC) for Nose-to-Brain Delivery Using the Quality by Design (QbD) Approach: Formulation Variables and Instrumental Parameters.

Rivastigmine is a drug commonly used in the management of Alzheimer's disease that shows bioavailability problems. To overcome this, the use of nanosystems, such as nanostructured lipid carriers (NLC), administered through alternative routes seems promising. In this work, we performed a double optimization of a rivastigmine-loaded NLC formulation for direct drug delivery from the nose to the brain using the quality by design (QbD) approach, whereby the quality target product profile (QTPP) was the requisite for nose to brain delivery. The experiments started with the optimization of the formulation variables (or critical material attributes-CMAs) using a central composite design. The rivastigmine-loaded NLC formulations with the best critical quality attributes (CQAs) of particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were selected for the second optimization, which was related to the production methods (ultrasound technique and high-pressure homogenization). The most suitable instrumental parameters for the production of NLC were analyzed through a Box-Behnken design, with the same CQAs being evaluated for the first optimization. For the second part of the optimization studies, were selected two rivastigmine-loaded NLC formulations: one produced by ultrasound technique and the other by the high-pressure homogenization (HPH) method. Afterwards, the pH and osmolarity of these formulations were adjusted to the physiological nasal mucosa values and in vitro drug release studies were performed. The results of the first part of the optimization showed that the most adequate ratios of lipids and surfactants were 7.49:1.94 and 4.5:0.5 (%, w/w), respectively. From the second part of the optimization, the results for the particle size, PDI, ZP, and EE of the rivastigmine-loaded NLC formulations produced by ultrasound technique and HPH method were, respectively, 114.0 ± 1.9 nm and 109.0 ± 0.9 nm; 0.221 ± 0.003 and 0.196 ± 0.007; -30.6 ± 0.3 mV and -30.5 ± 0.3 mV; 97.0 ± 0.5% and 97.2 ± 0.3%. Herein, the HPH was selected as the most suitable production method, although the ultrasound technique has also shown effectiveness. In addition, no significant changes in CQAs were observed after 90 days of storage of the formulations at different temperatures. In vitro studies showed that the release of rivastigmine followed a non-Fickian mechanism, with an initial fast drug release followed by a prolonged release over 48 h. This study has optimized a rivastigmine-loaded NLC formulation produced by the HPH method for nose-to-brain delivery of rivastigmine. The next step is for in vitro and in vivo experiments to demonstrate preclinical efficacy and safety. QbD was demonstrated to be a useful approach for the optimization of NLC formulations for which specific physicochemical requisites can be identified.

Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging.

Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (1). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC50 values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl3 and CuCl2) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone (1) was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone (1) was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.

Identification and Quantification of Stilbenes (Piceatannol and Resveratrol) in Passiflora edulis By-Products.

Recently, studies on the by-products from the food industry, such as passion fruit seeds, have significantly increased, as these can have an added value, due to their properties, such as potential antioxidant activity. This study was conducted to determine the presence of piceatannol and resveratrol in various extracts of passion fruit (Passiflora edulis) seeds from Madeira Island and a commercial passion fruit oil was used as reference. The commercial oil and the extracts that were obtained by traditional Soxhlet method with ethanol and acetone did not reveal the presence of the two stilbenes, piceatannol and resveratrol. However, the extracts that were obtained by the ultrasound method showed significant amounts of piceatannol and resveratrol when compared with the commercial oil. The presence of these compounds indicates that this oil could have potential application in cosmetic and pharmaceutical industries, due to their proven antioxidant and anti-aging properties.