RESUMO
Microemulsions are optically nanosized emulsions, isotropic and thermodynamically stable. They represent versatile drug delivery systems with high potential because they can be administered regardless of route. In the present study, we report on the formulation of a microemulsion made with glycerol (2.25%), Labrasol (20.25%) vitamin E acetate (2.50%), and water (75.00%), which was developed using the pseudo-ternary phase diagram. Globules of the microemulsion had PdI less than 0.25 and size of about 17 nm, evaluated by DLS analysis. These values did not change after loading khellin, a natural lipophilic molecule with interesting biological activities, used as a model of lipophilic drug. Carboxymethyl cellulose was selected as gelling polymer to obtain a microemulgel. Viscosity was 22â100.0 ± 1555.6 mPas·s at 21 ± 2â°C, while it was 8916.5 ± 118.1 mPas·s at 35 ± 2â°C, remaining stable over time. Khellin recovery was 93.16 ± 4.39% and was unchanged after 4 weeks of storage (93.23 ± 2.14%). The pH was 6.59 ± 0.19 and it was found to be 6.42 ± 0.34 at the end of the storage lifetime. The diffusion of khellin from the developed formulation was prolonged over an extended period. Based on overall results and due to the dermatological properties of the ingredients of the formulation, the developed microemulgel loaded with khellin is very promising and suitable for skin care applications.
Assuntos
Quelina , Tensoativos , Solubilidade , Sistemas de Liberação de Medicamentos/métodos , Veículos Farmacêuticos , EmulsõesRESUMO
Olea europaea L. leaves contain a wide variety of pentacyclic triterpenes (TTPs). TTPs exhibit many pharmacological activities, including antihyperlipidemic effects. Metabolic alterations, such as dyslipidemia, are an established risk factor for hepatocellular carcinoma (HCC). Therefore, the use of TTPs in the adjunctive treatment of HCC has been proposed as a possible method for the management of HCC. However, TTPs are characterized by poor water solubility, permeability, and bioavailability. In this work, a microemulsion (ME) loading a TTP-enriched extract (EXT) was developed, to overcome these limits and obtain a formulation for oral administration. The extract-loaded microemulsion (ME-EXT) was fully characterized, assessing its chemical and physical parameters and release characteristics, and the stability was evaluated for two months of storage at 4 °C and 25 °C. PAMPA (parallel artificial membrane permeability assay) was used to evaluate the influence of the formulation on the intestinal passive permeability of the TTPs across an artificial membrane. Furthermore, human hepatocarcinoma (HepG2) cells were used as a cellular model to evaluate the effect of EXT and ME-EXT on de novo lipogenesis induced by elevated glucose levels. The effect was evaluated by detecting fatty acid synthase expression levels and intracellular lipid accumulation. ME-EXT resulted as homogeneous dispersed-phase droplets, with significantly increased EXT aqueous solubility. Physical and chemical analyses showed the high stability of the formulation over 2 months. The formulation realized a prolonged release of TTPs, and permeation studies demonstrated that the formulation improved their passive permeability. Furthermore, the EXT reduced the lipid accumulation in HepG2 cells by inhibiting de novo lipogenesis, and the ME-EXT formulation enhanced the inhibitory activity of EXT on intracellular lipid accumulation.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Olea , Triterpenos , Humanos , Triterpenos Pentacíclicos , Lipogênese , Células Hep G2 , Carcinoma Hepatocelular/tratamento farmacológico , Emulsões/química , Neoplasias Hepáticas/tratamento farmacológico , Triterpenos/farmacologia , Triterpenos/química , Membranas Artificiais , Folhas de Planta , LipídeosRESUMO
In recent years, the interest in cannabidiol (CBD) has increased because of the lack of psychoactive properties. However, CBD has low solubility and bioavailability, variable pharmacokinetics profiles, poor stability, and a pronounced presystemic metabolism. CBD nanoformulations include nanosuspensions, polymeric micelles and nanoparticles, hybrid nanoparticles jelled in cross-linked chitosan, and numerous nanosized lipid formulations, including nanostructured lipid carriers, vesicles, SNEEDS, nanoemulsions, and microemulsions. Nanoformulations have resulted in high CBD solubility, encapsulation efficiency, and stability, and sustained CBD release. Some studies assessed the increased Cmax and AUC and decreased Tmax. A rational evaluation of the studies reported in this review evidences how some of them are very preliminary and should be completed before performing clinical trials. Almost all the developed nanoparticles have simple architectures, are well-known and safe nanocarriers, or are even simple nanosuspensions. In addition, the conventional routes of administration are generally investigated. As a consequence, many of these studies are almost ready for forthcoming clinical translations. Some of the developed nanosystems are very promising for a plethora of therapeutic opportunities because of the versatility in terms of the release, the crossing of physiological barriers, and the number of possible routes of administration.
Assuntos
Canabidiol , Quitosana , Nanopartículas , Administração Oral , Disponibilidade Biológica , Canabidiol/farmacocinética , Quitosana/metabolismo , Lipídeos , Micelas , Nanopartículas/metabolismo , SolubilidadeRESUMO
Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in the Oleaceae family, and it represents 3.5% of the dry weight of olive leaves. OA has many pharmacological activities, such as hepatoprotection, anti-inflammatory, anti-oxidant, anti-diabetic, anti-tumor, and anti-microbic activities. Its therapeutic application is limited by its poor water solubility, bioavailability, and permeability. In this study, solid dispersions (SDs) were developed to overcome these OA limitations. Solubility studies were conducted to evaluate different hydrophilic polymers, drug-to-polymer ratios, and preparation methods. Poloxamer 188, Poloxamer 407, and γ-CD exhibited the highest increases in terms of OA solubility, regardless of the method of preparation. Binary systems were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). In addition, pure compounds and SDs were analyzed using scanning electron microscopy (SEM) in order to observe both the morphology and the particle surface. In vitro dissolution studies were performed for P407, P188, and γ-CD SDs. Preparation using the solvent evaporation method (SEM) produced the highest increase in the dissolution profiles of all three polymers with respect to the OA solution. Finally, the effect of SDs on OA permeability was evaluated with an in vitro parallel artificial membrane permeability assay (PAMPA). The formulation improved passive permeation across the simulated barrier due to OA increased solubility. The dissolution and PAMPA results indicate that the amorphization of OA by SD preparation could be a useful method to enhance its oral absorption, and it is also applicable on an industrial scale.
Assuntos
Ácido Oleanólico , Poloxâmero , Varredura Diferencial de Calorimetria , Ácido Oleanólico/farmacologia , Permeabilidade , Poloxâmero/química , Polímeros/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios XRESUMO
The novel Regulation 2017/745/EC on medical devices introduces and strengthens the role of "medical devices made of substances", which mostly include substances of natural origin. Natural products may follow different regulations, from food to therapeutics. Concerning their isolated constituents, extracts are characterized by a complexity that is not easily tackled from both a scientific and a regulatory point of view, but more importantly, from a therapeutic point of view. The evidence-based approach applied to isolated molecules requires appropriate evidence of quality, efficacy, and safety. The same needs must be reached for complex substances by finding appropriate methods to generate this evidence, and in addition, defining an appropriate regulatory field for them. From a scientific point of view, new methods, such as those proposed by systems biology, are available and applicable to complex substances. From a regulatory point of view, Directive 2001/83/EC on medicinal products seems to be modeled on single (or combinations of single) molecule products. On the other hand, Regulation 2017/745/EC on medical devices seems to apply to complex substances without derogating on quality, efficacy, and safety. The regulation specifically names and strengthens medical devices that include substances, mostly of natural origin, introducing the official term "medical devices made of substances". This paper discusses and proposes an interpretation of important terms connected to this legislation, regarding both scientific and regulatory issues, and the opportunities the regulation may give for innovation and therapeutic improvement with natural complex substances.
Assuntos
Produtos BiológicosRESUMO
Food poisoning is a common cause of illness and death in developing countries. Essential oils (EOs) could be effective and safe natural preservatives to prevent and control bacterial contamination of foods. However, their high sensitivity and strong flavor limit their application and biological effectiveness. The aim of this study was firstly the chemical analysis and the antimicrobial evaluation of the EOs of Origanum onites L. and Satureja thymbra L. obtained from Symi island (Greece), and, secondly, the formulation of propylene glycol-nanovesicles loaded with these EOs to improve their antimicrobial properties. The EOs were analyzed by GC-MS and their chemical contents are presented herein. Different nanovesicles were formulated with small average sizes, high homogeneity, and optimal ζ-potential. Microscopic observation confirmed their small and spherical shape. Antibacterial and antifungal activities of the formulated EOs were evaluated against food-borne pathogens and spoilage microorganisms compared to pure EOs. Propylene glycol-nanovesicles loaded with O. onites EO were found to be the most active formulation against all tested strains. Additionally, in vitro studies on the HaCaT cell line showed that nanovesicles encapsulated with EOs had no toxic effect. The present study revealed that both EOs can be used as alternative sanitizers and preservatives in the food industry, and that their formulation in nanovesicles can provide a suitable approach as food-grade delivery system.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Nanopartículas , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Origanum/química , Satureja/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Fenômenos Químicos , Doenças Transmitidas por Alimentos/tratamento farmacológico , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Compostos FitoquímicosRESUMO
A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin's bioavailability and therapeutic effects.
Assuntos
Cannabis , Quelina , Nanoestruturas/química , Extratos Vegetais , Administração Oral , Células CACO-2 , Cannabis/química , Humanos , Quelina/química , Quelina/farmacocinética , Quelina/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Ácidos Esteáricos/química , Ácidos Esteáricos/farmacocinética , Ácidos Esteáricos/farmacologiaRESUMO
Bacopa monnieri (L.) is widely used in Ayurvedic medicine as a neural tonic for improving intelligence and memory. Several studies highlighted its efficacy in neuropsychiatric diseases but there is no evidence regarding anhedonia. Aim of the present work was to preclinically and clinically test against anhedonia a standardized B. monnieri extract (20% bacosides). In a mouse model of a depressive-like syndrome induced by lipopolysaccharide (LPS), the daily administration of the extract (50-200 mg kg-1 , p.o.) for 1 week, dose-dependently counteracted the immobility time in Porsolt and Tail suspension tests (p < .01). At the sucrose preference test (directly related to the ability for feeling pleasure) the extract treatment (100 and 200 mg kg-1 ) counteracted the reduction of sucrose intake induced by LPS (p < .01). Moreover, B. monnieri significantly reduced cytokines, cortisol, and artemin LPS-dependent alterations in plasma while increased the brain-derived neurotrophic factor levels (p < .05). The efficacy of the same extract was tested in a clinical study in which 42 patients with significant degree of anhedonia (evaluated as Snaith-Hamilton Pleasure Scale [SHAPS] score ≥ 3) were enrolled. Patients were divided into two groups and treated with citalopram or citalopram associated with B. monnieri (300 mg bid) for 4 weeks. The Pears Sample T-test showed a significant improvement (p < .05) in relevant scales (Hamilton depression rating scale, SHAPS, and strength and difficulties questionnaire) in the extract-treated group in comparison to citalopram alone was recorded. These data suggest that B. monnieri extract may be effective for the management of anhedonia and therefore should be considered for future controlled trials.
Assuntos
Anedonia/efeitos dos fármacos , Bacopa/química , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
Essential oils are complex mixtures of strongly active compounds, very volatile and sensitive to light, oxygen, moisture and temperature. Loading inside nanocarriers can be a strategy to increase their stability and successfully use them in therapy. In the present study, a commercial Melissa officinalis L. (Lamiaceae) essential oil (MEO) was analyzed by gas chromatography-mass spectrometry, loaded inside glycerosomes (MEO-GS) and evaluated for its anti-herpetic activity against HSV type 1. MEO-GS analyses were prepared by the thin layer evaporation method and they were characterized by light scattering techniques, determining average diameter, polydispersity index and ζ-potential. By transmission electron microscopy, MEO-GS appeared as small nano-sized vesicles with a spherical shape. MEO encapsulation efficiency inside glycerosomes, in terms of citral and ß-caryophyllene, was found to be ca. 63% and 76% respectively, and MEO release from glycerosomes, performed by dialysis bag method, resulted in less than 10% within 24h. In addition, MEO-GS had high chemical and physical stability during 4 months of storage. Finally, MEO-GS were very active in inhibiting HSV type 1 infection of mammalian cells in vitro, without producing cytotoxic effects. Thus, MEO-GS could be a promising tool in order to provide a suitable anti-herpetic formulation.
Assuntos
Antivirais , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/metabolismo , Melissa/química , Óleos Voláteis , Animais , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Chlorocebus aethiops , Herpes Simples/metabolismo , Herpes Simples/patologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Células VeroRESUMO
Targeted isolation based on a combination of NMR and HPLC-PDA-MS of a dichloromethane extract of Thymus vulgaris Varico 3 aerial parts afforded one new p-cymene dimer, 6,3',4'-trihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (1: ), together with two known p-cymene derivatives (2: and 3: ), as well as five known compounds, namely, thymol (4: ), oleanolic acid (5: ), ursolic acid (6: ), cirsimaritin (7: ), and xanthomicrol (8: ). The structural elucidation of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR, and HRESIMS experiments. The biphenyls were assayed for their inhibitory activity on tyrosinase. Compounds 2: and 3: showed negligible activity on tyrosinase, while compound 1: effectively inhibited the enzyme with 35% (± 0.3) inhibitory activity, higher than the inhibition of the reference compound kojic acid (18.6 ± 0.02).
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectroscopia de Ressonância Magnética/métodos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monoterpenos/isolamento & purificação , Extratos Vegetais/química , Thymus (Planta)/química , Flavonas/farmacologia , Monoterpenos/farmacologia , Ácido Oleanólico/farmacologia , Timol/farmacologia , Triterpenos/farmacologia , Ácido UrsólicoRESUMO
Malaria treatment and control have become increasingly difficult because of the spread of drug-resistant strains of Plasmodium falciparum and Plasmodium vivax. Thus, there is a continuous need to develop new combination therapies such as artemisinin-based combination therapies (ACTs) to contrast the emergence of resistant Plasmodium strains. Despite ACT has been recommended by the World Health Organization since 2001, its overall deployment in poor endemic areas is very slow, principally due to its high cost. In the malaria endemic areas, plant remedies are still widely used mostly without assurance of their efficacy and/or safety. A variety of widespread herbal drugs or natural products were already reported for their possible plasmodicidal activities, but the studies concerning their activity in combination with artemisinins are very scarce. The antimalarial activity of papaya is mostly anecdotal, and the present study is aimed at investigating the antiplasmodial activity of a decoction obtained by traditional recipe from the mature leaves of Carica papaya. The decoction was analyzed by HPLC-DAD-MS (high performance liquid chromatography coupled with diodoarray detector and mass spectrometry) showing the presence of caffeoyl derivatives and di- and triglycosides of flavonols. The extract was found to be active against P. falciparum 3D7 strains with a synergism in the presence of artemisinin. In vivo activity against the murine malaria model of Plasmodium berghei was disclosed both for the dried extract alone (250, 500, and 750 mg/kg/d) and for its combination with artesunate (250 mg/kg/d papaya plus 10 mg/kg/d artesunate). This combination displayed the greatest antimalarial activity in terms of reduction of parasitemia and prevention of recrudescence in animals recovered from the infection.
Assuntos
Antimaláricos/uso terapêutico , Artesunato/uso terapêutico , Carica/química , Malária/tratamento farmacológico , Fitoterapia/métodos , Folhas de Planta/química , Preparações de Plantas/uso terapêutico , Plasmodium berghei/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Artesunato/administração & dosagem , Cromatografia Líquida de Alta Pressão , Quimioterapia Combinada , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Preparações de Plantas/administração & dosagem , RecidivaRESUMO
Neurological-related disorders are seen as an increasingly important aspect of welfare. While conventional medicine is still the mainstay for the treatment of these diseases, it is becoming apparent that patients are also seeking more natural and preventative interventions. Panax ginseng G115® and Ginkgo biloba GK501® extracts alone or in combination were used in two in vitro experimental models of primary cultures exposed to excitotoxicity: rat organotypic hippocampal slices exposed to either 5 µM kainic acid or 10 µM N-Methyl-d-aspartate for 24 hours, and mixed cortical cells exposed to 300 µM NMDA for 10 min. Cell death in the Cornu Ammonis areas CA3 or CA1 subregions of slices was quantified by measuring propidium iodide fluorescence, whereas in cortical cells, it was assessed by measuring the amount of lactate dehydrogenase. In slices, treatment with extracts alone or in combination significantly attenuated CA3 and CA1 damage induced by exposure to kainic acid or NMDA, respectively. A similar neuroprotective effect was observed in cortical cells exposed to NMDA. Analysis of cell signaling pathways found that the two extracts induced an increase of the phosphorylation and they reversed the decrease of phosphorylation of ERK1/2 and Akt induced by kainic acid and NMDA in organotypic hippocampal slices. These results suggest that P. ginseng G115® and G. biloba GK501® extracts may mediate their effects by activating phosphorylation of ERK1/2 and Akt signaling pathways, protecting against excitotoxicity-induced damage in in vitro models.
Assuntos
Encefalopatias , Ginkgo biloba/química , Fármacos Neuroprotetores , Panax/química , Extratos Vegetais , Animais , Encefalopatias/induzido quimicamente , Encefalopatias/tratamento farmacológico , Encefalopatias/metabolismo , Encefalopatias/patologia , Modelos Animais de Doenças , Feminino , Masculino , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
: To study new target-oriented molecules that are active against rheumatoid arthritis-dependent pain, new dual inhibitors incorporating both a carbonic anhydrase (CA)-binding moiety and a cyclooxygenase inhibitor (NSAID) were tested in a rat model of rheumatoid arthritis induced by CFA intra-articular (i.a.) injection. A comparison between a repeated per os treatment and a single i.a. injection was performed. CFA (50 µL) was injected in the tibiotarsal joint, and the effect of per os repeated treatment (1 mg kg-1) or single i.a injection (1 mg ml-1, 50 µL) with NSAIDs-CAIs hybrid molecules, named 4 and 5, was evaluated. The molecules 4 and 5, which were administered daily for 14 days, significantly prevented CFA-induced hypersensitivity to mechanical noxious (Paw pressure test) and non-noxious stimuli (von Frey test), the postural unbalance related to spontaneous pain (Incapacitance test) and motor alterations (Beam balance test). Moreover, to study a possible localized activity, 4 and 5 were formulated in liposomes (lipo 4 and lipo 5, both 1 mg ml-1) and directly administered by a single i.a. injection seven days after CFA injection. Lipo 5 decreased the mechanical hypersensitivity to noxious and non-noxious stimuli and improved motor coordination. Oral and i.a. treatments did not rescue the joint, as shown by the histological analysis. This new class of potent molecules, which is able to inhibit at the same time CA and cyclooxygenase, shows high activity in a preclinical condition of rheumatoid arthritis, strongly suggesting a novel attractive pharmacodynamic profile.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Acetaminofen/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Experimental/genética , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Inibidores da Anidrase Carbônica/administração & dosagem , Anidrases Carbônicas/genética , Modelos Animais de Doenças , Adjuvante de Freund/administração & dosagem , Humanos , Inflamação/genética , Inflamação/patologia , Injeções Intra-Articulares , Dor/genética , Dor/patologia , Manejo da Dor/métodos , RatosRESUMO
Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin. Polymeric nanomicelles made of Soluplus and mixed nanomicelles combining Soluplus with d-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) were prepared using the thin film method. Physicochemical parameters were investigated, in particular the average diameter, the homogeneity (expressed as polydispersity index), the zeta potential, the morphology, the encapsulation efficiency, the drug loading, the critical micellar concentration and the cloud point. The sizes of ~60 nm, the narrow size distribution (polydispersity index ≤0.1) and the encapsulation efficiency >92% indicated the high affinity between silymarin and the core of the nanomicelles. Solubility studies demonstrated that the solubility of silymarin increased by ~6-fold when loaded into nanomicelles. Furthermore, the physical and chemical parameters of SLM-loaded formulations stored at room temperature and in refrigerated conditions (4 °C) were monitored over three months. In vitro stability and release studies in media miming the physiological conditions were also performed. In addition, both formulations did not alter the antioxidant properties of silymarin as evidenced by the 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) assay. The potential of the nanomicelles to increase the intestinal absorption of silymarin was firstly investigated by the parallel artificial membrane permeability assay. Subsequently, transport studies employing Caco-2 cell line demonstrated that mixed nanomicelles statistically enhanced the permeability of silymarin compared to polymeric nanomicelles and unformulated extract. Finally, the uptake studies indicated that both nanomicellar formulations entered into Caco-2 cells via energy-dependent mechanisms.
Assuntos
Portadores de Fármacos/química , Composição de Medicamentos , Micelas , Nanopartículas/química , Silimarina/administração & dosagem , Silimarina/química , Administração Oral , Disponibilidade Biológica , Células CACO-2 , Permeabilidade da Membrana Celular , Fenômenos Químicos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Microscopia Eletrônica , Tamanho da Partícula , Polímeros , Silimarina/farmacocinética , Solubilidade , TemperaturaRESUMO
Artemisia annua essential oil has given us many encouraging results for its numerous antimicrobial properties. In this study, the essential oil, both in liquid and in vapor phases, was tested against various Malassezia species closely related to many skin disorders in humans and animals. Malassezia treatment and eradication are mainly based on old azole drugs, which are characterized by poor compliance, unpredictable clinical efficacy, emerging resistance, and several side effects. Monoterpenes (ca. 88%) represent the most abundant group of compounds in the essential oil, mainly the oxygenated derivatives (ca. 74%) with camphor (25.2%), 1,8-cineole (20%), and artemisia ketone (12.5%). In vapor phase, monoterpenes represent more than 98% of the constituents, α-pinene being the main constituent (22.8%), followed by 1,8-cineole (22.1%) and camphene (12.9%). Essential oil of A. annua, both in vapor phase and liquid, showed strong antimicrobial activity towards almost the tested twenty strains of Malassezia analyzed. The minimum fungicidal concentrations from most of the strains tested were from 0.78 µL/mL to 1.56 µL/mL, and only three strains of Malassezia sympodialis required a higher concentration of 3.125 µL/mL. Overall, the minimal inhibitor concentrations obtained by vapor diffusion assay were lower than those obtained by the liquid method. The average values of minimal inhibitor concentrations obtained by the two methods at 72 h are 1.3â-â8.0 times higher in liquid compared to those in the vapor phase.
Assuntos
Antifúngicos/farmacologia , Artemisia annua/química , Malassezia/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Antifúngicos/química , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos de Plantas/química , Especificidade da EspécieRESUMO
A microemulsion system was developed and investigated as a novel oral formulation to increase the solubility and absorption of Salicis cortex extract. This extract possesses many pharmacological activities, in particular, it is beneficial for back pain and osteoarthritic and rheumatic complaints. In this work, after qualitative and quantitative characterization of the extract and the validation of an HPLC/diode array detector analytical method, solubility studies were performed to choose the best components for microemulsion formulation. The optimized microemulsion consisted of 2.5 g of triacetin, as the oil phase, 2.5 g of Tween 20 as the surfactant, 2.5 g of labrasol as the cosurfactant, and 5 g of water. The microemulsion was visually checked, characterized by light scattering techniques and morphological observations. The developed formulation appeared transparent, the droplet size was around 40 nm, and the ζ-potential result was negative. The maximum loading content of Salicis cortex extract resulted in 40 mg/mL. Furthermore, storage stability studies and an in vitro digestion assay were performed. The advantages offered by microemulsion were evaluated in vitro using artificial membranes and cells, i.e., parallel artificial membrane permeability assay and a Caco-2 model. Both studies proved that the microemulsion was successful in enhancing the permeation of extract compounds, so it could be useful to ameliorate the bioefficacy of Salicis cortex.
Assuntos
Álcoois Benzílicos/farmacocinética , Glucosídeos/farmacocinética , Extratos Vegetais/farmacocinética , Salix/química , Tensoativos/farmacocinética , Álcoois Benzílicos/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Emulsões , Flavanonas/química , Flavanonas/farmacocinética , Glucosídeos/química , Glicerídeos , Humanos , Membranas Artificiais , Permeabilidade/efeitos dos fármacos , Extratos Vegetais/química , Polissorbatos , Salicilatos/química , Salicilatos/farmacocinética , Ácido Salicílico/química , Ácido Salicílico/farmacocinética , Solubilidade/efeitos dos fármacos , Tensoativos/químicaRESUMO
The aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. ß-carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4â°C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30â-â70% passive oral human absorption in vivo.
Assuntos
Dióxido de Carbono/administração & dosagem , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanotecnologia , Serenoa/química , beta Caroteno/administração & dosagem , Administração Oral , Emulsões , HumanosRESUMO
Flower of Abelmoschus manihot (FAM) is clinically effective to treat chronic kidney disease (CKD) with a relatively high dosage. To improve the efficacy and the compliance of patients, macroporous resins were adopted to enrich and purify flavonoids from FAM, which are thought to be the major renal protective constituents in FAM. After screening six different kinds of macroporous resins, HPD-100 was selected for its great adsorption and desorption capacity. Then, orthogonal design tests were used to optimize parameters in the processes of impurity removal and flavonoids of FAM desorption on column chromatogram. Moreover, process scale-up was performed, and purification effects maintained after amplification. After purification, the content of seven main flavonoids in the product increased from 8.29% to 51.43%. Protective and anti-inflammatory effects of crude extract and the flavonoid component of FAM after purification were investigated on the adriamycin-damaged HK-2 cells and lipopolysaccharide-stimulated Raw 264.7 cells models. Both bioactivities were improved greatly after purification for these two cell models. Therefore, the purification process had enriched the main bioactive constituents with potential alleviating kidney injury activities. The flavonoid component of FAM is worthy of being developed as an improved remedy for CKD with better patients' compliance.
Assuntos
Abelmoschus/química , Anti-Inflamatórios/isolamento & purificação , Doxorrubicina/efeitos adversos , Flavonoides/isolamento & purificação , Lipopolissacarídeos/efeitos adversos , Resinas Sintéticas/química , Adsorção , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Flavonoides/química , Flavonoides/farmacologia , Flores/química , Humanos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Porosidade , Células RAW 264.7RESUMO
Andrographis paniculata is a herbal drug of Asian traditional medicine largely employed for the treatment of several diseases. Recently, it has been introduced in Europe for the prophylactic and symptomatic treatment of common cold and as an ingredient of dietary supplements. The active principles are diterpenes with andrographolide as the main representative. In the present study, an analytical protocol was developed for the determination of the main constituents in the herb and preparations of A. paniculata. Three different extraction protocols (methanol extraction using a modified Soxhlet procedure, maceration under ultrasonication, and decoction) were tested. Ultrasonication achieved the highest content of analytes. HPLC conditions were optimized in terms of solvent mixtures, time course, and temperature. A reversed phase C18 column eluted with a gradient system consisting of acetonitrile and acidified water and including an isocratic step at 30â°C was used. The HPLC method was validated for linearity, limits of quantitation and detection, repeatability, precision, and accuracy. The overall method was validated for precision and accuracy over at least three different concentration levels. Relative standard deviation was less than 1.13%, whereas recovery was between 95.50% and 97.19%. The method also proved to be suitable for the determination of a large number of commercial samples and was proposed to the European Pharmacopoeia for the quality control of Andrographidis herba.
Assuntos
Andrographis/química , Diterpenos/normas , Medicina Herbária/normas , Extratos Vegetais/normas , Cromatografia Líquida de Alta Pressão , Diterpenos/química , Diterpenos/isolamento & purificação , Medicina Tradicional , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Controle de QualidadeRESUMO
Verbascoside (acteoside) possesses various pharmacological properties for human health, including antioxidant, anti-inflammatory, and antineoplastic properties in addition to numerous wound healing and neuroprotective properties, with an excellent and well-known safety profile. However, its poor chemical stability, due to hydrolysis, limits its use in the clinic. To overcome these limitations, we prepared unilamellar liposomal formulations of verbascoside for parenteral administration.Two formulations were prepared: V-L1 and V-L2, where V-L2 contains phospholipid and cholesterol about 4 times higher than the V-L1 sample, and about 2 times higher than verbascoside. The mean particle size of the liposomes prepared was found to be around 120 nm with a polydispersity index < 0.2. Encapsulation efficacy resulted in 30â%. A total of 82.28 ± 1.79â% of verbascoside was released from the liposomes within 24 hours. Liposomes ameliorate the stability of verbascoside by preventing its hydrolysis.The optimized drug delivery formulation was tested in the paw pressure test in two animal models of neuropathic pain: a peripheral mononeuropathy was produced either by a chronic constriction injury of the sciatic nerve or by an intra-articular injection of sodium monoiodoacetate. The performance of the liposomal formulation was compared with that of the free drug.For evaluating the paw pressure test in chronic constriction injury rats, a liposomal formulation administered i.âp. at the dosage of 100 mg/kg showed a longer lasting antihyperalgesic effect in comparison with a 100-mg/kg verbascoside saline solution, as well as in the sodium monoiodoacetate models. The effect appeared 15 min after administration and persisted for up to 60 min.