A Synthetic Model of the Mucosa for Oral Penetration Studies.

The main objective of this study is the evaluation of the use of a synthetic membrane, Nuclepore, as a model for permeation studies through sublingual mucosa. The permeability of two types of membranes, porcine sublingual oral mucosa and a synthetic Nuclepore membrane, to water was compared. Moreover, the water permeability of membranes modified with waterproofing formulations was measured to study their ability to protect against the penetration of viruses, toxins, etc. A relatively high correlation (R2 0.88) was obtained between the transmucosal water loss (TMWL) values of the artificial membrane and the mucosa. These results support the possible use of this synthetic membrane in the screening of the water permeability of formulations. In addition, studies of the permeation of different actives, drugs, and biocides through the two membranes were carried out, and these results were compared with their skin permeation data. The synthetic membrane does not seem to discern between compounds in terms of permeability. However, the permeation of caffeine through intact or modified membranes incorporating waterproofing formulations presents similar permeation profiles through the synthetic membrane and mucosa. The results from these assays should lend support to the use of this synthetic membrane when screening formulations to be applied in oral penetration studies.

Permeation Protection by Waterproofing Mucosal Membranes.

The permeability of the oral or nasal mucosa is higher than that of the skin. Mucosa permeability depends mainly on the thickness and keratinization degree of the tissues. Their permeability barrier is conditioned by the presence of certain lipids. This work has the main aim of reinforcing the barrier effect of oral mucosa with a series of formulations to reduce permeation. Transmembrane water loss of different formulations was evaluated, and three of them were selected to be tested on the sublingual mucosa permeation of drugs. Caffeine, ibuprofen, dexamethasone, and ivermectin were applied on porcine skin, mucosa, and modified mucosa in order to compare the effectiveness of the formulations. A similar permeation profile was obtained in the different membranes: caffeine > ibuprofen~dexamethasone > ivermectin. The most efficient formulation was a liposomal formulation composed of lipids that are present in the skin stratum corneum. Impermeability provided by this formulation was notable mainly for the low-molecular-weight compounds, decreasing their permeability coefficient by between 40 and 80%. The reinforcement of the barrier function of mucosa provides a reduction or prevention of the permeation of different actives, which could be extrapolated to toxic compounds such as viruses, contaminants, toxins, etc.

Development and characterization of a poloxamer hydrogel composed of human mesenchymal stromal cells (hMSCs) for reepithelization of skin injuries.

Wound healing is a natural physiological reaction to tissue injury. Hydrogels show attractive advantages in wound healing not only due to their biodegradability, biocompatibility and permeability but also because provide an excellent environment for cell migration and proliferation. The main objective of the present study was the design and characterization of a hydrogel loaded with human mesenchymal stromal cells (hMSCs) for use in would healing of superficial skin injures. Poloxamer 407® was used as biocompatible biomaterial to embed hMSCs. The developed hydrogel containing 20 % (w/w) of polymer resulted in the best formulation with respect to physical, mechanical, morphological and biological properties. Its high swelling capacity confirmed the hydrogel's capacity to absorb wounds' exudate. LIVE/DEAD® assay confirm that hMSCs remained viable for at least 48 h when loaded into the hydrogels. Adding increasing concentrations of hMSCs-loaded hydrogel to the epithelium did not affect keratinocytes' viability and healing capacity and all wound area was closed in less than one day. Our study opens opportunities to exploit poloxamer hydrogels as cell carriers for the treatment of skin superficial wound.

Gel Formulations with an Echinocandin for Cutaneous Candidiasis: The Influence of Azone and Transcutol on Biopharmaceutical Features.

Caspofungin is a drug that is used for fungal infections that are difficult to treat, including invasive aspergillosis and candidemia, as well as other forms of invasive candidiasis. The aim of this study was to incorporate Azone in a caspofungin gel (CPF-AZ-gel) and compare it with a promoter-free caspofungin gel (CPF-gel). An in vitro release study using a polytetrafluoroethylene membrane and ex vivo permeation into human skin was adopted. The tolerability properties were confirmed by histological analysis, and an evaluation of the biomechanical properties of the skin was undertaken. Antimicrobial efficacy was determined against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. CPF-AZ-gel and CPF-gel, which had a homogeneous appearance, pseudoplastic behavior, and high spreadability, were obtained. The biopharmaceutical studies confirmed that caspofungin was released following a one-phase exponential association model and the CPF-AZ gel showed a higher release. The CPF-AZ gel showed higher retention of caspofungin in the skin while limiting the diffusion of the drug to the receptor fluid. Both formulations were well-tolerated in the histological sections, as well as after their topical application in the skin. These formulations inhibited the growth of C. glabrata, C. parapsilosis, and C. tropicalis, while C. albicans showed resistance. In summary, dermal treatment with caspofungin could be used as a promising therapy for cutaneous candidiasis in patients that are refractory or intolerant to conventional antifungal agents.

Caspofungin-Loaded Formulations for Treating Ocular Infections Caused by Candida spp.

Fungal keratitis causes corneal blindness worldwide. The treatment includes antibiotics, with Natamycin being the most commonly used; however, fungal keratitis is difficult to treat, so alternative therapies are needed. In situ gelling formulations are a promising alternative; this type of formulation has the advantages of eye drops combined with the advantages of ointments. This study was designed to develop and characterize three formulations containing 0.5% CSP: CSP-O1, CSP-O2, and CSP-O3. CSP is an antifungal drug that acts against a diverse variety of fungi, and Poloxamer 407 (P407) is a polymer of synthetic origin that is able to produce biocompatible, biodegradable, highly permeable gels and is known to be thermoreversible. Short-term stability showed that formulations are best stored at 4 °C, and rheological analysis showed that the only formulation able to gel in situ was CSP-O3. In vitro release studies indicated that CSP-O1 releases CSP most rapidly, while in vitro permeation studies showed that CSP-O3 permeated the most. The ocular tolerance study showed that none of the formulations caused eye irritation. However, CSP-O1 decreased the cornea's transparency. Histological results indicate that the formulations are suitable for use, with the exception of CSP-O3, which induced slight structural changes in the scleral structure. All formulations were shown to have antifungal activity. In view of the results obtained, these formulations could be promising candidates for use in the treatment of fungal keratitis.

Preparation and ex vivo investigation of an injectable microparticulate formulation for gastrointestinal mucosa polyp resection.

Endoscopic submucosal dissection (ESD) and endoscopic submucosal resection (EMR) are non-invasive endoscopic techniques. They allow an early excised gastrointestinal (GI) mucosal precancerous lessions. For their application is necessary to use a submucosal injection that lifts the area to excise. The main objective of this study was the preparation of a microparticulate-based fluid for injection in the GI submucosa. Alginate microparticles (MPs) were developed by the solvent displacement technique and characterized by particle size, surface electrical properties, swelling, degradation, rheology, adhesion, leakage, syringeablity and stability. Furthermore, their potential to form a submucosal cushion was assayed in porcine stomach mucosa and porcine colon mucosa. Results showed MPs sizes below 160 µm, negative surface charge around -50 mV at pH = 6, high rates of swelling and good adhesion. The microparticulate-based fluid exhibited pseudoplastic behavior following the Ostwald-de Waele rheological model. A brief force is sufficient for its injection through a syringe. Finally, formulations were able to provide a submucosa elevation of 1.70 cm for more than 90 min and 120 min in the porcine stomach and colon, respectively.

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.

Novel Polymeric Formulation for Removal of Gastrointestinal Polyps by Digestive Endoscopy.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are two techniques used in the resection of gastrointestinal mucosal polyps. The aim of this work is the development and evaluation of an innovative polymeric solution containing sodium carboxymethylcellulose and hyaluronic acid. For this purpose, several mixtures of these two main components, as well as other components such as fructose, citric acid, and zinc, are evaluated in terms of physicochemical and microbiological properties, rheological behavior, extensibility, syringeability, and stability at different storage conditions. Furthermore, the potential production of mucosal elevation and duration is also studied by an ex vivo model using porcine stomach and colon. Results show that the developed polymeric solutions possess optimal values of pH, from 4.58 to 6.63, for their use in the gastrointestinal tract. The formulations exhibit both Newtonian and pseudoplastic behaviors with different viscosity values as a function of their composition. All formulations exhibit high stability properties and no bacterial or fungal growth is detected. MCS01 and MCS05 are the polymeric solutions with the best syringeability results. In this line, MCS05 is the formulation that provides the highest, 2.20 ± 0.18 cm and 1.40 ± 0.11 cm, and longest-lasting, for more than 120 min, elevation effect on porcine submucosal stomach and colon tissues, respectively. Thus, it can be concluded that polymeric solution MCS05 might be considered as a promising tool for use in human EMR and ESD.

Efficacy and Safety of a Novel Submucosal Injection Solution for Resection of Gastrointestinal Lesions.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are minimally invasive and efficient techniques for the removal of gastrointestinal (GI) mucosal polyps. In both techniques, submucosal injection solutions are necessary for complete effectiveness and safety during the intervention to be obtained. The main objective of this study was to evaluate the efficacy and safety of a new sterile submucosal injection solution for EMR/ESD used within a clinical protocol in patients with intestinal polyps. We carried out a prospective study between 2016 and 2017 with patients who attended the Endoscopy Consultation-Digestive Department of Primary Hospital. Patients were selected for EMR/ESD after the application of clinical protocols. Thirty-six patients were selected (≥ 66 years with comorbidities and risk factors). Lesions were located mainly in the colon. Our solution presented an intestinal lift ≥ 60 min in EMR/ESD and a high expansion of tissue, optimum viscosity, and subsequent complete resorption. The genes S100A9 and TP53 presented an expression increase in the distal regions. TP53 and PCNA were the only genes whose expression was increased in polyp specimens vs. the surrounding tissue at the mRNA level. In EMR/ESD, our solution presented a prolonged effect at the intestinal level during all times of the intervention. Thus, our solution seems be an effective and safe alternative in cases of flat lesions in both techniques.

Design and evaluation of a multifunctional thermosensitive poloxamer-chitosan-hyaluronic acid gel for the treatment of skin burns.

The main goal of this study was the design, development and characterization of a poloxamer/chitosan/hyaluronic based vehicle including three biological antioxidant molecules such as vitamins A, D and E aimed at improving the treatment of skin burns. The physical characterization of hydrogel, its mechanical and rheological properties as well as internal structure were investigated. Furthermore, biological characteristics such as ex vivo antimicrobial properties and in vivo wound healing were also accomplished and compared with a commercial reference. Results showed optimal physicochemical properties with biocompatible pH value of 4.6 ±â€¯0.1 and zeta potential dependent on pH. The swelling rate was around 350% with optimal wettability, adhesion and leakage properties, as well as thermosensitive gelation processes. The microbiological assay demonstrated similar antimicrobial activity to that of commercial reference. In vivo tolerance study revealed no skin reactions. Finally, the wound healing efficacy of hydrogel in skin burn model showed dermal appendages and similar epidermis, dermis and stratum corneum to the commercial reference. These findings indicated that our hydrogel loading vitamins could be considered an outstanding candidate for further clinical studies.

Design and evaluation of mesenchymal stem cells seeded chitosan/glycosaminoglycans quaternary hydrogel scaffolds for wound healing applications.

The main goal of this study was the design, development and characterization of a chitosan based scaffolding substrate including three glycosaminoglycans and collagen to provide an optimal microenvironment for human mesemchymal stem cells isolated from adipose tissue (hMSCs). Chitosan scaffolds provide a moist wound environment which promotes healing and epidermal regeneration. Furthermore, the importance of extracellular molecules such as glycosaminoglycans in wound healing makes them essential ingredients in these types of formulations. The physical properties of hydrogels scaffolds and stability were investigated. The scaffolds were evaluated by structural and microscopic assays, as well as cell culture analyses. The hydrogel with best suitable properties was selected as candidate scaffold for hMSCs encapsulation. The viability of hMSCs remained above 75%, indicating good cell viability. The number of living hMSCs in the scaffold reached a steady state up to ~100% at days 5 and 7. Scanning electron microscopy showed irregular compartments with the presence of the hMSCs. These findings indicated that our hydrogel scaffold provided a suitable niche for cell viability which could be considered a promising candidate for further in vivo studies.

Biopharmaceutical Development of a Bifonazole Multiple Emulsion for Enhanced Epidermal Delivery.

Efficient topical delivery of imidazolic antifungals faces the challenge of overcoming its limited water solubility and its required long-lasting duration of treatments. In this paper, a hydrophilic multiple emulsion (ME) of Bifonazole (BFZ) is shown to maximize its skin retention, minimize its skin permeation, and maintain an acceptable level of being harmless in vivo. The formulations were pharmaceutically characterized and application properties were assessed based on viscosity measurements. Non-Newtonian pseudoplastic shear thinning with apparent thixotropy was observed, facilitating the formulation retention over the skin. The in vitro release profile with vertical diffusion cells showed a predominant square-root release kinetic suggesting an infinite dose depletion from the formulation. Ex vivo human skin permeation and penetration was additionally evaluated. Respective skin permeation was lower than values obtained with a commercial O/W formulation. The combination of amphoteric and non-ionic surfactants increased the bifonazole epidermal accumulation by a factor of twenty. This fact makes the possibility of increasing its current 24 h administration frequency more likely. Eventual alterations of skin integrity caused by the formulations were examined with epidermal histological analysis and in vivo preclinical measurements of skin elasticity and water retrograde permeation. Histological analysis demonstrated that the multiple emulsions were harmless. Additionally, modifications of in vivo skin integrity descriptors were considered as negligible.

Clotrimazole multiple W/O/W emulsion as anticandidal agent: Characterization and evaluation on skin and mucosae.

Clotrimazole (CLT) was formulated in a multiple W/O/W emulsion (ME) with the aim of evaluating its potential as topical anticandidal agent and comparing with marketed products. A previously evaluated CLT-ME was selected and physicochemically characterized. The in vitro release behavior and the ex vivo permeation profiles were assessed using Franz diffusion cells using three different types of biological membranes: human skin and porcine buccal, sublingual and vaginal mucosae. The antifungal activity against Candida strains was also tested. Results showed CLT-MEs sizes of 29.206 and 47.678 µm with skin compatible pH values of 6.47 and 6.42 exhibiting high zeta potential values of -55.13 and -55.59 mV with dependence on the pH variation. The physicochemical stability was kept for a period of 180 days of storage at room temperature. CLT-MEs exhibited pseudoplastic behavior with hysteresis areas and viscosities of 286 and 331 mPa⋅s showing higher spreadability properties than commercial counterparts. An improved CLT release pattern was supplied by the ME system following a hyperbolic model. Likewise, ME system gave higher skin permeation flux of CLT than commercial reference. CLT amounts retained in the skin and mucosae were also higher than commercial references, which coupled with the higher antimycotic efficacy make CLT-MEs a great tool for clinical investigation of topical candidiasis treatments.

Biopharmaceutical profile of a clotrimazole nanoemulsion: Evaluation on skin and mucosae as anticandidal agent.

Clotrimazole (CLT) was formulated in a nanoemulsion (NE) for the topical treatment of candidiasis consisting of 10% labrafac® lipophile, 60% labrasol®:capryol® 90 mixture (ratio 4:1) and 30% propylene glycol. Physicochemical properties, stability, rheology, in vitro drug release, ex vivo drug permeation through human skin and porcine buccal, sublingual and vaginal mucosae, antifungal efficacy, as well as in vivo skin tolerance were evaluated. 1% CLT-NE (CLT-NE1) and 2% CLT-NE (CLT-NE2) exhibited 153 ±â€¯17.25 and 186 ±â€¯15.38 nm droplet sizes, low polydispersity indexes, negative zeta potentials and biocompatible pH values. The CLT-NEs exhibited typical Newtonian profiles with viscosities of 42.14 ±â€¯0.037 mPa·s and 41.35 ±â€¯0.041 mPa·s, respectively and higher extensibility properties than commercial counterparts retaining their physicochemical properties for 180 days. NEs provided a sustained release of drug according to the first order model. Similar skin permeation properties were observed between CLT-NE1 and commercial reference. However, significant higher CLT amounts retained in mucosae were provided by CLT-NE2 when compared with references. Antifungal efficacies were also higher than commercial references, and the in vivo tolerance study confirmed the suitability for topical application, making CLT-NEs a great tool for clinical investigation of topical candidiasis treatments.

Nano-engineering of biomedical prednisolone liposomes: evaluation of the cytotoxic effect on human colon carcinoma cell lines.

OBJECTIVES: Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. METHODS: Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. KEY FINDINGS: Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. CONCLUSIONS: This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents.

Development and characterization of two nano-structured systems for topical application of flavanones isolated from Eysenhardtia platycarpa.

Many of the inflammatory diseases are becoming common in ageing society throughout the world. The clinically used anti-inflammatory drugs suffer from the disadvantage of side effects. Alternative to these drugs are natural products, since ancient times traditional medicines are being used for the treatment of inflammation. In the present study, four flavanones isolated from Eysenhardtia platycarpa leaves with a potent pharmacological activity were formulated in effective drug delivery systems: nanoemulsion and polymeric nanoparticles for topical use as novel anti-inflammatory topical formulations. Nanoemulsion system exhibited droplet sizes less than 70 nm and polymeric nanoparticles with a size of 156-202 nm possessed zeta potential values less than -25 mV that provided good stability and obtained high entrapment efficiency (78-90%). In vitro release and ex vivo permeation studies were performed on Franz-type diffusion cells and quantified by high performance liquid chromatography (HPLC), all formulations showed steady state release profiles over time and steady increase of flavanones in the skin permeation test. The anti-inflammatory activity, tested by TPA (12-O-tetradecanoylphorbol-13-acetate), induced oedema in mice ear suggesting that prenylated flavanones improve significantly their anti-inflammatory activity when are vehiculized in nanosized systems. Our results suggested that 5-hydroxy-7-methoxy-6-prenyl flavanone loaded nanoemulsion and polymeric nanoparticle could be proposed as potential topical anti-inflammatory formulations with the best properties for the treatment of inflammatory disorders.

Study of the stability of packaging and storage conditions of human mesenchymal stem cell for intra-arterial clinical application in patient with critical limb ischemia.

Critical limb ischemia (CLI) is associated with significant morbidity and mortality. In this study, we developed and characterized an intra-arterial cell suspension containing human mesenchymal stem cells (hMSCs) for the treatment of CLI. Equally, the stability of cells was studied in order to evaluate the optimal conditions of storage that guarantee the viability from cell processing to the administration phase. Effects of various factors, including excipients, storage temperature and time were evaluated to analyze the survival of hMSCs in the finished medicinal product. The viability of hMSCs in different packaging media was studied for 60 h at 4 °C. The best medium to maintain hMSCs viability was then selected to test storage conditions (4, 8, 25 and 37 °C; 60 h). The results showed that at 4 °C the viability was maintained above 80% for 48 h, at 8 °C decreased slightly, whereas at room temperature and 37 °C decreased drastically. Its biocompatibility was assessed by cell morphology and cell viability assays. During stability study, the stored cells did not show any change in their phenotypic or genotypic characteristics and physicochemical properties remained constant, the ability to differentiate into adipocytes and osteocytes and sterility requirements were also unaltered. Finally, our paper proposes a packing media composed of albumin 20%, glucose 5% and Ringer's lactate at a concentration of 1×10(6) cells/mL, which must be stored at 4 °C as the most suitable to maintain cell viability (>80%) and without altering their characteristics for more than 48 h.

Formulation design and optimization for the improvement of nystatin-loaded lipid intravenous emulsion.

Nystatin (NYS) is a polyene macrolide with broad antifungal spectrum restricted to topical use owing to its toxicity upon systemic administration. The aims of this work were the design, development, and optimization of NYS-loaded lipid emulsion for intravenous administration. A closed circuit system was designed to apply ultrasound during the elaboration of the lipid intravenous emulsions (LIEs). Additionally, a comparison with the commercially available Intralipid(®) 20% was also performed. Manufacturing conditions were optimized by factorial design. Formulations were evaluated in terms of physicochemical parameters, stability, release profile, and antimicrobial activity. The average droplet size, polydispersity index, zeta-potential, pH, and volume distribution values ranged between 192.5 and 143.0 nm, 0.170 and 0.135, -46 and -44 mV, 7.11 and 7.53, 580 and 670 nm, respectively. The selected NYS-loaded LIE (NYS-LIE54) consisted of soybean oil (30%), soybean lecithin (2%), solutol HS(®) 15 (4%), and glycerol (2.25%) was stable for at least 60 days. In vitro drug release studies of this formulation suggested a sustained-release profile. Equally, NYS-LIE54 showed the best antimicrobial activity being higher than the free drug. Thus, it could be a promising drug delivery system to treat systemic fungal infections.

Análisis de sistemas bucoadhesivos / Analysis of bucoadhesive systems

Objetivo: El objetivo de este estudio es el diseño de un parche bucoadhesivo para la administración transbucal de clorhidrato de doxepina utilizando diferentes polímeros así como la caracterización de dichos sistemas en cuanto al análisis calorimétrico y la capacidad de hinchamiento. Materiales y métodos: Se ha utilizado clorhidrato de doxepina y diferentes polímeros, carboximetilcelulosa sódica, hidroxipropilmetilcelulosa y chitosan. La calorimetría diferencial de barrido (DSC) se ha realizado en un dispositivo Mettler FP 80 equipado con un horno FP 85 y la capacidad de hinchamiento utilizando placas de agar. Resultados: Se obtienen termogramas de los parches y las mezclas físicas donde se observan transiciones endotérmicas entre 30 y 120º C y el pico endotérmico del principio activo en las mezclas físicas binarias. La entalpía de deshidratación es similar en los polímeros de carboximetilcelulosa sódica y chitosan (281 J/g) siendo menor en la película de hidroxipropilmetilcelulosa (251 J/g), al igual que el porcentaje de hidratación donde se demuestra que los parches elaborados con hidroxipropilmetilcelulosa presenta menor tendencia a captar agua (55,91 %) frente al 67,04 % y 67,30 % de la carboximetilcelulosa sódica y chitosan, respectivamente. Conclusión: Los resultados obtenidos muestran que existe compatibilidad entre los componentes de la formulación y los datos de entalpía se correlacionan con los datos obtenidos en el ensayo de hinchamiento (AU)

Aim: The aim of this study is to design a bucoadhesive patch for the transbuccal administration of doxepin hydrochloride using different polymers as well as the characterization of these systems for calorimetric analysis and the swelling capacity. Materials and methods: Doxepin hydrochloride was used as well as various polymers; carboxymethylcellulose sodium, hydroxypropylmethyl cellulose and chitosan. Differential scanning calorimetry (DSC) was carried out using a Mettler FP 80 device equipped with a FP 85 oven and the swelling capacity using agar plates. Results: Thermograms obtained patches and physical mixtures where there are endothermic transitions between 30 and 120º C and the endothermic peak of the active principle in binary physical mixtures. Dehydration enthalpy is similar in polymers of carboxymethylcellulose sodium and chitosan (281 J/g), the film having less hydroxypropylmethylcellulose (251 J/g), the percentage of moisture shows that the patches prepared with hydroxypropylmethylcellulose have less tendency to collect water (55.91 %) compared to 67.04 % and 67.30 % with sodium carboxymethylcellulose and chitosan, respectively. Conclusion: The results show that there is compatibility between the components of the formulation and the enthalpy data correlate with the data obtained in the swelling test (AU)

Anti-inflammatory, antioxidant and cytotoxicity activities of methanolic extract and prenylated flavanones isolated from leaves of Eysehardtia platycarpa.

From the methanolic extract of Eysenhardtia platycarpa (leaves), were isolated the prenylated flavanones: 5,7-dihydroxy-6-methyl-8-prenylflavanone (1), 5,7-dihydroxy-6-methyl-8-prenyl-4'-methoxy-flavanone (2), 5,7-dihydroxy-6-prenylflavanone (3), 5-dihydroxy-7-methoxy-6-prenylflavanone (4), 5,7-dihydroxy-8-prenyl-4'-methoxy-flavanone (5). Methanolic extract of E. platycarpa (leaves) and flavanones (5), (2) and (3) showed anti-inflammatory activity according to tested quantities. In addition, flavanone (5) revealed the best percentage reduction of free radical DPPH. Finally, after cytotoxic activity study, the methanolic extract from E. platycarpa leaves and flavanone (4) exhibited promising cytotoxic activity on brine shrimp.