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.

A New Hyaluronic Emulgel of Hesperetin for Topical Application-An In Vitro Evaluation.

The present study aimed to formulate and characterize a hesperetin formulation to achieve adequate deposition and retention of hesperetin in the epidermis as a target for some cosmetic/dermatological actions. To derive the final emulgel, various formulations incorporating different proportions of Polysorbate 80 and hyaluronic acid underwent testing through a Box-Behnken experimental design. Nine formulations were created until the targeted emulgel properties were achieved. This systematic approach, following the principles of a design of experiment (DoE) methodology, adheres to a quality-by-design (QbD) paradigm, ensuring a robust and purposeful formulation and highlighting the commitment to a quality-driven design approach. The emulsions were developed using the phase inversion method, optimizing the emulgel with the incorporation of hyaluronic acid. Physically stable optimized emulgels were evaluated for their globule size, surface charge, viscosity, pH, electrical conductivity, and hesperetin content. These assays, along with the temperature swing test, were used to select the optimal formulation. It was characterized by a droplet size, d[4,3], of 4.02 µm, a Z-potential of -27.8 mV, an O/W sign, a pH of 5.2, and a creamy texture and proved to be stable for at least 2 months at room temperature. Additionally, in vitro release kinetics from the selected emulgel exhibited a sustained release profile of hesperetin. Skin assays revealed adequate retention of hesperetin in the human epidermis with minimum permeation. Altogether, these results corroborate the promising future of the proposed emulgel in cosmetic or dermatological use on healthy or diseased skin.

Intranasal Drug Administration in Alzheimer-Type Dementia: Towards Clinical Applications.

Alzheimer-type dementia (ATD) treatments face limitations in crossing the blood-brain barrier and systemic adverse effects. Intranasal administration offers a direct route to the brain via the nasal cavity's olfactory and trigeminal pathways. However, nasal physiology can hinder drug absorption and limit bioavailability. Therefore, the physicochemical characteristics of formulations must be optimized by means of technological strategies. Among the strategies that have been explored, lipid-based nanosystems, particularly nanostructured lipid carriers, are promising in preclinical investigations with minimal toxicity and therapeutic efficacy due to their ability to overcome challenges associated with other nanocarriers. We review the studies of nanostructured lipid carriers for intranasal administration in the treatment of ATD. Currently, no drugs for intranasal administration in ATD have marketing approval, with only three candidates, insulin, rivastigmine and APH-1105, being clinically investigated. Further studies with different candidates will eventually confirm the potential of the intranasal route of administration in the treatment of ATD.

New scenario in the field of medical devices in the European Union: Switzerland and the United Kingdom become third countries.

OBJECTIVE: To compare the measures taken by the European Union,  Switzerland and the United Kingdom to ensure the continuity of the medical  devices market, complying with the requirements of Regulation  2017/745. METHOD: To carry out this work, a review was made of the official websites of  the European Commission, the Spanish Agency for Medicines and Health  Products, the Swiss Agency for Therapeutic Products and the Medicines and  Healthcare Products Regulatory Agency of the United Kingdom. Bibliographic  searches were also conducted on Pubmed and the internet (Google), using  terms such as "withdrawal of the Mutual Recognition Agreement of Swiss  European Union medical device conformity certificates, new UK medical device  regulation", for a period extending from January 2020 to December 2021. RESULTS: As a result of the disappearance of the legal framework  that supported free trade between Switzerland, the United Kingdom and  the European Union, products that used to be unrestrictedly distributed in Europe have become imports having to comply with the relevant legal  requirements. Distributors for their part have become importers, and  declarations of conformity and CE certificates have lost their validity.  Furthermore, notified bodies from Switzerland and the United Kingdom are no  longer recognized by the European Commission. Switzerland, the United Kingdom and the European Union have had to grant grace periods to allow  regulatory agencies and economic operators to adapt to the new situation. CONCLUSIONS: The transition period toward the new economic scenario has not  yet ended. Both Switzerland and the United Kingdom have had to take  stronger measures than the EU to adapt to the changes. Both Switzerland and  the United Kingdom are expected to finally incorporate the requirements of the  new Regulation in their internal legal systems.

OBJETIVO: Comparar las medidas que se han tomado por parte de la Unión  Europea, Suiza y Reino Unido para mantener la continuidad de mercado  cumpliendo con los requisitos regulatorios del Reglamento 745/2017 de   productos Sanitarios.Método: Para realizar este trabajo se han revisado las webs oficiales de la  omisión Europea, la Agencia Española del Medicamento y Productos Sanitarios,  la Swiss Agency for Therapeutic Products y la Medicines and  Healthcare Products Regulatory Agency del Reino Unido y se han realizado  búsquedas bibliográficas en PubMed y en internet (Google) con términos como  "withdrawal Mutual Recognition Agreement of certificates of conformity  European Union Switzerland medical devices, new regulation medical devices  UK" y similares para un periodo comprendido entre enero de 2020 y diciembre  de 2021. RESULTADOS: Como resultado del cese del marco legal que sostenía el libre  comercio entre Suiza y Reino Unido de la Unión Europea, la distribución de  productos sanitarios se ha convertido en una importación, teniendo que  cumplir con los requisitos legales pertinentes. Los distribuidores han pasado a  ser importadores, y las declaraciones de conformidad y certificados de  Conformidad Europea han perdido su validez. Además, los Organismos  Notificados ya no son reconocidos por la Comisión EuroAbstract  pea. En  consecuencia, Suiza, Reino Unido y la Unión Europea han tenido que conceder  periodos de gracia para permitir a las agencias reguladoras y operadores  conómicos adaptarse a las nuevas condiciones. CONCLUSIONES: El periodo de transición para la adaptación al nuevo escenario económico todavía no ha concluido. Además, el Reglamento acaba de entrar plenamente en vigor, por lo que se creará normativa de desarrollo que deberá implementarse también en estos países. Por tanto, será necesaria una nueva reglamentación que permita abordar estos aspectos.

American and European legislation on border medical devices.

INTRODUCTION: Borderline medical devices are products in a 'gray area,' this means due to their characteristics, they could belong to different 'legal products.' In addition, regulation is a controversial topic and may change depending on the country which may put public health at risk and distort the market. AREAS COVERED: This article analyzes how borderline medical devices are managed in the American and the European legislation. We compared the decisions made by both regulations on the devices of the Manual on Borderline and Classification Medical Devices of the European Commission for the first three sections, those which deal exclusively with medical devices. EXPERT OPINION: Borderline medical devices do not have to be understood as something specific to each country. The different classification of products creates international borders. It is necessary to create working groups in international organizations in which global consensus is reached. Although a priori it seems that the American system could be more efficient, studies with quantitative data from authorized devices are needed to show that. Until EUDAMED is not fully operational and open access, it will not be possible to develop them.

Borderline products do not have a simple product classification and can be managed differently depending on different countries. The different classification between countries has economic consequences for companies and patients. In this article, the American and European regulations system is compared, specifically borderline products, using as a tool the Borderline and Classification Manual of the European Commission. Results show the international consensus is necessary to avoid barriers to trade and contribute to innovation. Although both regulations have points of improvement, with the data from the Manual (EU), it seems that American regulatory system could be more efficient, although copying some of its strengths could be complicated due to the intrinsic characteristics of the European system. However, studies with quantitative data are needed to corroborate this statement.

Nanoliposomes in Cancer Therapy: Marketed Products and Current Clinical Trials.

The drugs used for cancer treatment have many drawbacks, as they damage both tumor and healthy cells and, in addition, they tend to be poorly soluble drugs. Their transport in nanoparticles can solve these problems as these can release the drug into tumor tissues, as well as improve their solubility, bioavailability, and efficacy, reducing their adverse effects. This article focuses on the advantages that nanotechnology can bring to medicine, with special emphasis on nanoliposomes. For this, a review has been made of the nanoliposomal systems marketed for the treatment of cancer, as well as those that are in the research phase, highlighting the clinical trials being carried out. All marketed liposomes studied are intravenously administered, showing a reduced intensity of side-effects compared with the nonliposomal form. Doxorubicin is the active ingredient most frequently employed. Ongoing clinical trials expand the availability of liposomal medicines with new clinical indications. In conclusion, the introduction of drugs in nanoliposomes means an improvement in their efficacy and the quality of life of patients. The future focus of research could be directed to develop multifunctional targeted nanoliposomes using new anticancer drugs, different types of existing drugs, or new standardized methodologies easily translated into industrial scale.

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.

Formulation of liposomes loading lentisk oil to ameliorate topical delivery, attenuate oxidative stress damage and improve cell migration in scratch assay.

Pistacia lentiscus L. is a sclerophyllous shrub capable of growing under harsh climatic conditions especially in the Mediterranean Basin. Different products can be obtained from this plant, such as essential oil, mastic gum or even fixed oil. The last is well known for its flavor which is mainly exploited in the food industry. Additionally, it has been traditionally used in the treatment of skin diseases, but, at the moment, any suitable formulation for skin delivery has been formulated and its biological effects was not deeply confirmed. Given that, in the present study, the lentisk oil has been formulated in liposomes at different concentrations (10, 20, 30 mg/ml) and their physicochemical, technological and main biological properties have been evaluated. Vesicles were prepared by using natural soy lecithin and a green and organic solvent free method, thus obtaining spherical, small (~ 118 nm), homogeneously dispersed (0.27) and highly negatively charged (~ -62 mV) vesicles. The used amount of oil loaded in liposomes (10, 20, 30 mg/ml) modulated the penetration ability of vesicles in the skin, favoring the deposition of the payload in the deeper strata. The loading in the vesicles potentiated the ability of oil to counteract the damaging effects caused by hydrogen peroxide in keratinocytes and fibroblasts and facilitate their migration in a cell monolayer lesion. Overall findings suggested that the incorporation of lentisk oil in liposomes made from soy lecithin can be an alternative and natural approach to exploit it in pharmaceutical ad cosmetical applications and manufacturing natural products suitable for the treatment of skin lesions.

Face masks against the background of the COVID 19 pandemic: legal considerations about their use.

OBJECTIVE: The objective of this article is to review the quality  equirements and recommended uses of the different types of face masks  with a view to helping optimize their use and facilitating identification of  nonconforming products. METHOD: A literature search was conducted in PubMed, the Spanish Official State Gazette and Eudralex. The websites of the Ministry of Industry, Commerce and Tourism and of the Ministry of Health, as well as  the relevant UNE standards were also reviewed. RESULTS: The different types of face masks available on the market meet different regulatory requirements. Community masks are not  considered medical devices or personal protective equipment and do not  require marketing authorization. They do not carry a CE mark and need  not comply with the general regulations applicable to consumer products.  Surgical masks, for their part, must meet the quality criteria defined in  UNE-EN standard 14683: 2019. According to Regulation (EU) 745/2017  they are class I devices, subject to an EU declaration of conformity, and  must bear a CE mark. Filtering masks are considered category III personal protective equipment, regulated by Regulation (EU) 2016/425, and must  also bear a CE mark. In spite the abundant regulations in place, market  control instruments have detected counterfeit face masks, which means  that public authorities and users should ask manufacturers or suppliers for  additional information in case of doubt. CONCLUSIONS: The legal and quality requirements of the masks are  sufficient for their safe use. It is necessary for the general public to know  these requirements to avoid the fraudulent use of high consumption  products.

Objetivo: Revisar los requisitos de calidad y usos recomendados de los diferentes tipos de mascarillas con objeto de optimizar su uso y facilitar la identificación de los productos no conformes.Método: Se hizo una búsqueda bibliográfica en PubMed, en el Boletín Oficial del Estado y Eudralex; se revisaron las páginas web de los  Ministerios de Industria, Comercio y Turismo y Sanidad, así como las  normas UNE.Resultados: Los diferentes tipos de mascarillas que se pueden encontrar en el mercado se acogen a diferentes exigencias regulatorias.  Las mascarillas higiénicas no se consideran productos sanitarios ni equipo de protección individual y no necesitan autorización. No llevan  marcado CE y deben cumplir con la normativa general de los productos de  consumo. Para las mascarillas quirúrgicas, los criterios de calidad están  definidos en la UNE-EN 14683:2019, son productos sanitarios de clase I  según el Reglamento (UE) 745/2017, se les requiere declaración UE de  conformidad y debe colocar el marcado CE en el producto. Las mascarillas  filtrantes son equipos de protección individual de categoría III, están  reguladas por el Reglamento (UE) 2016/425 y deben llevar marcado CE  conforme al mismo. Por otro lado, los instrumentos de control de mercado  han detectado mascarillas fraudulentas, por ello, ante cualquier duda se  debe solicitar información adicional al fabricante o proveedor.Conclusiones: Los requisitos legales y de calidad de las mascarillas son  suficientes para su uso seguro. Es necesario que el público general conozca estos requisitos para evitar el uso fraudulento de estos  productos de alto consumo.

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.

Co-loading of finasteride and baicalin in phospholipid vesicles tailored for the treatment of hair disorders.

Hair loss affects a large number of people worldwide and it has a negative impact on the quality of life. Despite the availability of different drugs for the treatment of hair disorders, therapeutic options are still limited and scarcely effective. An innovative strategy to improve the efficacy of alopecia treatment is presented in this work. Finasteride, the only oral synthetic drug approved by Unites States Federal Drug Administration, was loaded in phospholipid vesicles. In addition, baicalin was co-loaded as an adjuvant. Their effect on hair growth was evaluated in vitro and in vivo. Liposomes, hyalurosomes, glycerosomes and glycerol-hyalurosomes were manufactured by using a simple method that avoids the use of organic solvents. All the vesicles were small in size (∼100 nm), homogeneously dispersed (polydispersity index ≤0.27) and negatively charged (∼-16 mV). The formulations were able to stimulate the proliferation of human dermal papilla cells, which are widely used in hair physiology studies. The analysis of hair growth and hair follicles of C57BL/6 mice, treated with the formulations for 21 days, underlined the ability of the vesicles to improve hair growth by the simultaneous follicular delivery of finasteride and baicalin. Therefore, the developed nanosystems can represent a promising tool to ensure the efficacy of the local treatment of hair loss.

Innovative strategies to treat skin wounds with mangiferin: fabrication of transfersomes modified with glycols and mucin.

Aim: The moisturizing properties of glycerol, the penetration enhancing capability of propylene glycol and the bioadhesive properties of mucin were combined to improve the carrier capabilities of transfersomes and the efficacy of mangiferin in the treatment of skin lesions. Materials & methods: Mangiferin was incorporated in transfersomes and glycoltransfersomes, which were also modified with mucin. The physico-chemical features were assessed, along with the efficacy against oxidative stress and skin wounds in vitro and in vivo. Results: Glycoltransfersomes promoted the deposition of mangiferin in epidermis and dermis, protected fibroblasts from oxidative stress and stimulated their proliferation. The wound healing and anti-inflammatory efficacy of glycoltransfersomes were confirmed in vivo. Conclusion: Results confirmed the potential of glycoltransfersomes in preventing/treating of skin lesions.

Mangiferin glycethosomes as a new potential adjuvant for the treatment of psoriasis.

Mangiferin, a natural compound isolated from Mangifera indica L, was incorporated in glycerosomes, ethosomes and alternatively in glycerol-ethanol phospholipid vesicles (glycethosomes). Actually, only glycethosomes were able to stably incorporate the mangiferin that was loaded at increasing concentrations (2, 4, 6, 8 mg/mL). The morphology, size distribution, rheological properties, surface charge and entrapment efficiency of prepared vesicles were deeply measured. All vesicles were mainly spherical, oligolamellar, small in size (~145 nm) and negatively charged (~-40 mV), as confirmed by cryo-TEM observation and dynamic laser light scattering measurements. The higher concentration of mangiferin (8 mg/mL) allowed an increase of vesicle mean diameter up to ~288 nm. The entrapment efficiency was inversely proportional to the amount of loaded mangiferin. In vitro studies performed by using human abdominal skin, underlined that, the dose-dependent ability of vesicles to promote mangiferin retention in epidermis. In addition, glycethosomes were highly biocompatible and showed a strong ability to protect in vitro the fibroblasts against damages induced by hydrogen peroxide. In vivo results underlined the superior ability of mangiferin loaded glycethosomes respect to the mangiferin dispersion to promote the heal of the wound induced by TPA, confirming their potential application for the treatment of psoriasis or other skin disorders.

Eco-scalable baicalin loaded vesicles developed by combining phospholipid with ethanol, glycerol, and propylene glycol to enhance skin permeation and protection.

A new class of biocompatible and scalable phospholipid vesicles was developed, aiming at improving the efficacy of baicalin on the skin. Phosphatidylcholine and baicalin (a natural polyphenol) were hydrated in two steps with a mixture of ethanol, glycerol, and propylene glycol at different ratios, and a low amount of water (4%). Hence, water was almost completely replaced by the co-solvents, which were never used before as predominant dispersing medium of phospholipid vesicles. The vesicles appeared three-dimensionally structured, forming a network that conferred a high viscosity to the dispersions. The vesicles were unilamellar, small in size (∼100 nm), and stable during 12 months of storage. They disclosed optimal performances in the transdermal delivery of baicalin, and high biocompatibility with skin cells (i.e., keratinocytes and fibroblasts). Furthermore, the vesicles promoted the efficacy of baicalin in protecting skin cells against oxidative stress in vitro and injured skin in vivo.

Mangiferin nanoemulsions in treatment of inflammatory disorders and skin regeneration.

In this paper mangiferin nanoemulsions were developed using hyaluronic acid of different molecular weight, in absence or presence of Transcutol-P. An extensive study was carried out on the physico-chemical properties of nanoemulsions. Nanosizer and transmission electron microscopy showed oil droplets average size 296 nm with monodisperses distribution (PI ≤ 0.30). The zeta potential was highly negative (-30 mV). FTIR analysis confirms the existence of physical interactions among compounds. Rheological measurements allowed to conclude that all formulations present a pseudoplastic behavior (s ∼ 0.4) in presence of the biopolymer. Moreover, mangiferin release depends on the molecular weight of the polymer. Permeability assays on pig epidermis showed that nanoemulsions with low molecular weight hyaluronic acid improve the permeation, being this effect more pronounced in nanoemulsions with Transcutol-P. Administration of mangiferin nanoemulsions on TPA-inflamed skin mice model provided an attenuation of oedema and leucocyte infiltration. Macroscopic appearance of mice skin lesions has a good correlation with the histological study. The topical application of these formulations shows an appropriate anti-inflammatory effect.

Co-Loading of Ascorbic Acid and Tocopherol in Eudragit-Nutriosomes to Counteract Intestinal Oxidative Stress.

The present study aimed at developing a new vesicular formulation capable of promoting the protective effect of ascorbic acid and tocopherol against intestinal oxidative stress damage, and their efficacy in intestinal wound healing upon oral administration. A pH-dependent copolymer (Eudragit® L100), a water-soluble prebiotic fibre (Nutriose® FM06), a phospholipid mixture (Lipoid S75), and two natural antioxidants (ascorbic acid and tocopherol) were combined to fabricate eudragit-nutriosomes by a simple, solvent-free procedure. The vesicles were spherical and oligolamellar, with some multicompartment structures in Eudragit-nutriosomes, small in size (~100 nm), with highly negative zeta potential. The effect of Eudragit® and Nutriose® on the stability on storage and in simulated gastrointestinal fluids were confirmed by the Turbiscan® technology and in vitro studies, respectively. Eudragit-nutriosomes exhibited a protective effect against H2O2-induced oxidative stress, and a proliferative effect in Caco-2 cells, as they provided the closure of the scratched area after 96 h of incubation.

A novel lidocaine hydrochloride mucoadhesive films for periodontal diseases.

Periodontal diseases are inflammatory disorders caused primarily by dental plaque microorganisms that even may need surgery to remove damaged tissue. Adhesive biocompatible films may be an adequate form in order to improve drug retention or prevent microbial infections by covering the surgical site. In recent years, much attention has been focused on biocompatible inexpensive polymers, for biomedical and pharmaceutical potential applications. The objective of this research is the development of a film for mucosal application containing lidocaine hydrochloride (5%, w/w) as anesthetic drug. Lidocaine films were prepared with three biopolymers: hydroxypropylmethylcellulose (HPMC), chitosan (CH), or xanthan gum (XG). Their thickness and uniformity content were characterized. Rheological behavior of the hydrated films was studied using flow curves, creep and recovery tests and dynamic oscillatory measurements with a rheometer. The mucoadhesive assays were carried out with cheeks of Wistar rat using a universal tensile tester to know their adhesiveness. Finally, lidocaine delivery through the films was investigated in Franz cells. All films (n = 3 for each polymer) showed flexibility, a drug content of 0.015 ± 0.001 g/cm2 and a thickness of 0.25 ± 0.01 mm. The results of the maximum detachment force in tensile tests and work adhesion indicated that XG is the polymer that showed greater power of mucoadhesion (p < 0.05). These properties show a good correlation with the rheological characteristics. In all cases, the lidocaine amount released at 30 min is around 4 mg/cm2. This amount could be considered sufficient to guarantee the anesthetic effect.

Sorbitol-penetration enhancer containing vesicles loaded with baicalin for the protection and regeneration of skin injured by oxidative stress and UV radiation.

Aiming at improving the protective effects of baicalin on the skin, new highly-biocompatible penetration enhancer containing vesicles (PEVs) were developed by modifying the base formulation of transfersomes with sorbitol, thus obtaining sorbitol-PEVs. An extensive evaluation of the physico-chemical features of both transfersomes and sorbitol-PEVs was carried out. Transfersomes were mainly close-packed, multi-compartment vesicles, while sorbitol-PEVs appeared mostly as single, spherical, unilamellar vesicles. All the vesicles were small in size (∼128 nm) and negatively charged (∼-67 mV), without significant differences between the formulations. The in vitro delivery of baicalin to intact skin showed an improved ability of sorbitol-PEVs to favour the deposition of the flavonoid into the whole skin. In addition, the vesicular formulations protected keratinocytes and fibroblasts from oxidative stress and UV radiation, and promoted cell proliferation and migration, which favoured the closure of skin wound. Cell uptake was promoted as well, especially when sorbitol-PEVs were used.

Baicalin and berberine ultradeformable vesicles as potential adjuvant in vitiligo therapy.

0.5-1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distribution, surface charge and entrapment efficiency were assessed. The ability of the vesicles to promote the permeation of the polyphenols was evaluated. The antioxidant and photoprotective effects were investigated in vitro using keratinocytes and fibroblasts. Further, the stimulation of melanin production and tyrosinase activity in melanocytes after treatment with the vesicles were assessed. Ultradeformable vesicles were small in size, homogeneously dispersed, and negatively charged. They were able to incorporate high amounts of baicalin and berberine, and promote their skin permeation. In fact, the polyphenols concentration in the epidermis was higher than 10%, which could be indicative of the formation of a depot in the epidermis. The vesicles showed remarkable antioxidant and photoprotective capabilities, presumably correlated with the stimulation of melanin production and tyrosinase activity. In conclusion, baicalin or berberine ultradeformable vesicles, and particularly their combination, may represent promising nanosystem-based adjuvants for the treatment of vitiligo symptoms.

Tocopherol-loaded transfersomes: In vitro antioxidant activity and efficacy in skin regeneration.

Transfersomes were prepared by using different polysorbates (i.e., Tween 20, 40, 60 and 80) and loaded with tocopherol acetate, a naturally-occurring phenolic compound with antioxidant activity. The vesicles showed unilamellar morphology, small size (∼85 nm), low polydispersity index (≤0.27), and high entrapment efficiency, which increased as a function of the length of the Tween fatty acid chain (from 72% to 90%). The long-term stability of the formulations was evaluated by means of the Turbiscan™ technology, which indicated their good stability, irrespective of the Tween used. The vesicles efficiently delivered tocopherol to the skin, and showed biocompatibility in vitro in keratinocytes and fibroblasts. Regardless of the Tween used, the transfersomes were able to protect skin cells from the oxidative damage induced by hydrogen peroxide. Additionally, transfersomes promoted cell proliferation and migration, which resulted in an acceleration of skin wound closure. These results demonstrated that tocopherol-loaded transfersomes bear potential as topical delivery system with antioxidant activity and wound healing properties.