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1.
Chem Biodivers ; 21(6): e202400159, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563619

RESUMO

While the flowers of Matricaria recutita L., German chamomile, are widely used for medicinal and cosmetic purposes, little is known about its roots, which are used in complementary medicine for the preparation of aqueous fermented extracts for the treatment of cramps and anxiety. To broaden the understanding of the active principles involved, a model fermentation approach was developed and fermentates were compared to commercially manufactured tinctures. Coumarins and hydroxycinnamates were among the major secondary metabolites characterized using HPLC-MSn. After six months of fermentation and storage, low-molecular organic acids were detected by GC-MS. Fermentation contributed to the stabilization of antioxidant and radical scavenging activities, which were in a range of about 8-10 mg gallic acid equivalents/g dry weight and 20-24 mg trolox equivalents/g dry weight, determined by Folin-Ciocalteu and DPPH assays, respectively. In addition, antibacterial activities of the extracts against Gram-positive and -negative bacteria increased during the first week of fermentation. Fermentates were neither cytotoxic nor pro- or anti-inflammatory. Thus, fermentation of chamomile roots is a suitable method for the safe production of biofunctional aqueous chamomile root extracts that remain stable without the addition of synthetic preservatives.


Assuntos
Antioxidantes , Fermentação , Matricaria , Compostos Fitoquímicos , Extratos Vegetais , Raízes de Plantas , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Matricaria/química , Matricaria/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Testes de Sensibilidade Microbiana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Água/química , Animais , Picratos/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos
2.
Molecules ; 29(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38930889

RESUMO

The Equisetaceae family, commonly known as horsetails, has been of scientific interest for decades due to its status as one of the most ancient extant vascular plant families. Notably, the corresponding species have found their place in traditional medicine, offering a wide array of applications. This study presents a comprehensive phytochemical analysis of polar secondary metabolites within the sterile stems of five distinct Equisetum species using HPLC-DAD-ESI-MSn. For this purpose, fresh plant material was extracted with acetone/water, and the resulting crude extracts were fractionated using dichloromethane, ethyl acetate, and n-butanol, respectively. The results reveal a complex array of compounds, including hydroxycinnamic acids, hydroxybenzoic acids, flavonoids, and other phenolic compounds. In addition, total phenolic contents (Folin-Ciocalteu assay) and antioxidant activities (DPPH assay) of the plant extracts were evaluated using spectrophotometric methods. The present comparative analysis across the five species highlights both shared and species-specific metabolites, providing valuable insights into their chemical diversity and potential pharmacological properties.


Assuntos
Antioxidantes , Equisetum , Compostos Fitoquímicos , Extratos Vegetais , Caules de Planta , Antioxidantes/química , Antioxidantes/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química , Equisetum/química , Caules de Planta/química , Cromatografia Líquida de Alta Pressão , Fenóis/química , Fenóis/análise , Flavonoides/química , Flavonoides/análise
3.
MAGMA ; 35(3): 401-410, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34698962

RESUMO

OBJECTIVE: To provide a basis for the selection of suitable emulsifiers in oil-in-water emulsions used as tissue analogs for MRI experiments. Three different emulsifiers were investigated with regard to their ability to stabilize tissue-like oil-in-water emulsions. Furthermore, MR signal properties of the emulsifiers themselves and influences on relaxation times and ADC values of the aqueous phase were investigated. MATERIALS AND METHODS: Polysorbate 60, sodium dodecyl sulfate (SDS) and soy lecithin were used as emulsifiers. MR characteristics of emulsifiers were assessed in aqueous solutions and their function as a stabilizer was examined in oil-in-water emulsions of varying fat content (10, 20, 30, 40, 50%). Stability and homogeneity of the oil-in-water emulsions were evaluated with a delay of 3 h and 9 h after preparation using T1 mapping and visual control. Signal properties of the emulsifiers were investigated by 1H-MRS in aqueous emulsifier solutions. Relaxometry and diffusion weighted MRI (DWI) were performed to investigate the effect of various emulsifier concentrations on relaxation times (T1 and T2) and ADC values of aqueous solutions. RESULTS: Emulsions stabilized by polysorbate 60 or soy lecithin were stable and homogeneous across all tested fat fractions. In contrast, emulsions with SDS showed a significantly lower stability and homogeneity. Recorded T1 maps revealed marked creaming of oil droplets in almost all of the emulsions with SDS. The spectral analysis showed several additional signals for polysorbate and SDS. However, lecithin remained invisible in 1H-MRS. Relaxometry and DWI revealed different influences of the emulsifiers on water: Polysorbate and SDS showed only minor effects on relaxation times and ADC values of aqueous solutions, whereas lecithin showed a strong decrease in both relaxation times (r1,lecithin = 0.11 wt.%-1 s-1, r2,lecithin = 0.57 wt.%-1 s-1) and ADC value (Δ(ADC)lecithin = - 0.18 × 10-3 mm2/s⋅wt.%) with increasing concentration. CONCLUSION: Lecithin is suggested as the preferred emulsifier of oil-in-water emulsions in MRI as it shows a high stabilizing ability and remains invisible in MRI experiments. In addition, lecithin is suitable as an alternative means of adjusting relaxation times and ADC values of water.


Assuntos
Lecitinas , Polissorbatos , Emulsificantes , Emulsões , Imageamento por Ressonância Magnética , Tamanho da Partícula , Água
4.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142179

RESUMO

The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities. However, stress conditions imposed during common pharmaceutical processing (e.g., tableting) may cause the recrystallization of the systems, warranting close stability monitoring throughout production. This work aimed at assessing the water and heat stability of amorphous olanzapine (OLZ) and OLZ-CAMs when subject to wet granulation and pelletization. Starting materials and products were characterized using calorimetry, diffractometry and spectroscopy, and their performance behavior was evaluated by dissolution testing. The results indicated that amorphous OLZ was reconverted back to a crystalline state after exposure to water and heat; conversely, OLZ-CAMs stabilized with saccharin (SAC), a sulfonic acid, did not show any significant loss of the amorphous content, confirming the higher stability of OLZ in the CAM. Besides resistance under the processing conditions of the dosage forms considered, OLZ-CAMs presented a higher solubility and dissolution rate than the respective crystalline counterpart. Furthermore, in situ co-amorphization of OLZ and SAC during granule production with high fractions of water unveils the possibility of reducing production steps and associated costs.


Assuntos
Sacarina , Água , Cristalização , Estabilidade de Medicamentos , Olanzapina , Solubilidade , Ácidos Sulfônicos , Comprimidos , Água/química , Difração de Raios X
5.
Molecules ; 27(23)2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36500602

RESUMO

Matricaria recutita L., German chamomile, is one of the most widely used medicinal plants, whose efficacy has been proven in numerous studies. However, its roots have attracted only little interest so far, since mainly above-ground plant parts are used for medicinal purposes. To broaden the knowledge of chamomile roots, a profound phytochemical characterization was performed along with a bioactivity screening of corresponding root extracts. While volatile constituents such as chamomillol and polyynes were detected using GC-MS, HPLC-MSn analyses revealed the occurrence of four coumarin glycosides, more than ten phenolic acid esters and five glyceroglycolipids. Furthermore, the antioxidant activity of the extracts was evaluated. Polar extracts revealed IC50 values ranging from 13 to 57 µg/mL in the DPPH radical scavenging assay, which is in the same range as reported for chamomile flower extracts. In addition, superoxide radical scavenging potential and mild antibacterial effects against S. aureus und B. subtilis were demonstrated. Moreover, to assess interspecies variation in chamomile roots, extracts of M. recutita were compared to those of M. discoidea DC. Interestingly, the latter revealed stronger antioxidant activity. The presented results aim at the valorization of chamomile roots, previously discarded as by-product of chamomile flower production, as a sustainable source of bioactive phytochemicals.


Assuntos
Matricaria , Óleos Voláteis , Matricaria/química , Antioxidantes/farmacologia , Staphylococcus aureus , Óleos Voláteis/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química
6.
AAPS PharmSciTech ; 22(6): 205, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34286391

RESUMO

Drug-loaded electrospun fibers have attracted increasing attention as a promising wound dressing material due to their capability of preventing from infections and inflammation and maintaining an appropriate environment for wound healing. In this study, polylactic acid (PLA), which is widely used in wound management, was chosen as electrospinnable polymer. A triterpene extract (TE) from the outer bark of birch known for its anti-inflammatory, antiviral, antibacterial, and wound healing effects was chosen to produce TE-loaded PLA electrospun fibers for wound dressing. A binary solvent system of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) was employed, and the ratio of the solvents was optimized for preparing smooth and uniform fibers. The morphology of TE-loaded PLA electrospun fibers was investigated by scanning electron microscopy (SEM). The entrapment of TE in PLA fibers was confirmed by confocal laser scanning microscopy (CLSM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze the solid state of TE in PLA fibers. The release behavior of TE was assayed by a shaking flask method for a period of 96 h. The results revealed that TE-loaded electrospun PLA microfibers could be reliably prepared and are promising future candidates in wound therapy.


Assuntos
Bandagens , Betula/química , Nanofibras/química , Casca de Planta/química , Poliésteres/síntese química , Triterpenos/síntese química , Antibacterianos/análise , Antibacterianos/síntese química , Química Farmacêutica/métodos , Nanofibras/análise , Extratos Vegetais/análise , Extratos Vegetais/síntese química , Poliésteres/análise , Triterpenos/análise
7.
Drug Dev Ind Pharm ; 46(11): 1753-1762, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33006298

RESUMO

OBJECTIVE: Probiotic bacteria, such as different lactobacilli strains, have successfully been used to treat gingivitis and periodontitis or caries. By formulating probiotics as orodispersible tablet (ODT), the benefits of this dosage form could be utilized. Without any further measures, the probiotic bacteria will be eliminated too fast from the intended site of action, the oral mucosa. The use of mucoadhesive granules, composed of mucoadhesive polymer and probiotics, is a promising strategy to prolong the contact time between lactobacilli and oral mucosa without delaying disintegration. METHODS: Three common mucoadhesive polymers, anionic Carbopol 971P NF, nonionic Metolose 65SH50 and cationic chitosan were included into tablets either by direct compression (DC) or after granulation with the probiotics. Disintegration, mucoadhesion of the tablets, and storage stability of the probiotics were characterized. RESULTS: By incorporating a sufficient amount of polymer superior probiotic mucoadhesion could be achieved. All formulations based on granulated probiotics and mucoadhesive polymer fulfilled the Food and Drug Administration (FDA) acceptance level for disintegration of orodispersible tablets. These formulations exhibited excellent storage stability under refrigerated conditions over 30 months. Interestingly, ODTs including Carbopol 971P NF still proved superior mucoadhesion after long-term storage, whereas the mucoadhesive effect of Metolose 65SH50 and chitosan declined markedly. CONCLUSIONS: The results of this study suggest that Carbopol 971P NF was the most appropriate polymer for a probiotic mucoadhesive ODT.


Assuntos
Polímeros/química , Probióticos , Adesividade , Administração Bucal , Mucosa Bucal/efeitos dos fármacos , Comprimidos
8.
Drug Dev Ind Pharm ; 46(7): 1185-1198, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32536225

RESUMO

Objective: The development of medicinal plants for clinical use represents an important direction in biomedical research, despite the technological difficulties.Significance: The aim of this study was to compare pharmaceutical characteristics and in vitro release of Classical and Pickering emulsions containing crude or fractionated extracts of Libidibia ferrea.Methods: After evaluating the extract's solubility in formulation, a dispersion of hydroxypropyl methylcellulose (HPMC) was prepared in water. For Pickering emulsions, the aqueous phase was HPMC and the oil phase was Miglyol® 812; for Classical emulsions, water with Tween® 20 and Miglyol® 812 with Span® 80 were used for aqueous and oil phases, respectively. Crude or fractionated extracts were added to the aqueous phase (5% w/v). Both phases were heated (40 °C); then, the oil phase was poured into the aqueous phase and homogenized using an Ultra-Turrax. Emulsions were characterized for 90 days by pH, polyphenol content, phytomarker content, macroscopic characteristics, droplet size, and zeta potential.Results: These formulations displayed satisfactory stability for 90 days when stored at 25 °C. Regarding the investigation of rheological properties, Pickering emulsions displayed higher viscosity with lesser deformation than Classical emulsions. Moreover, the emulsions displayed similar in vitro release behavior.Conclusion: Based on the results of present study, the Pickering emulsions were obtainable and displayed higher stability than Classical emulsions. Additionally, maintenance of system integrity points to promising systems for delivery of active pharmaceutical ingredients in the internal phase, despite the complex chemical mixture added to the external phase.


Assuntos
Extratos Vegetais , Água , Emulsões , Tamanho da Partícula , Reologia
9.
Molecules ; 25(20)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086645

RESUMO

Triterpenes from the outer bark of birch (TE) are known for various pharmacological effects including enhanced wound healing. Apart from an already authorized oleogel, electrospun nanofiber mats containing these triterpenes in a polyvinyl alcohol (PVA) matrix appear to be an advantageous application form. The effects of PVA molecular weight and concentration on the fiber morphology have been investigated. Three different molecular weights of PVA ranging from 67 to 186 kDa were used. The concentration of PVA was varied from 5 to 20 wt%. Polymer solutions were blended with colloidal dispersions of birch bark extract at a weight ratio of 60:40 (wt.%). The estimated viscosity of polymer solutions was directly linked to their concentration and molecular weight. In addition, both pure and blended solutions showed viscoelastic properties with a dominant viscous response in the bulk. Fiber morphology was confirmed using scanning electron microscopy (SEM). Both polymer concentration and molecular weight were found to be significant factors affecting the diameter of the fibers. Fiber diameter increased with a higher molecular weight and polymer concentration as more uniform fibers were obtained using PVA of higher molecular weight (146-186 kDa). In vitro drug release and ex vivo permeation studies indicated a faster drug release of betulin from electrospun scaffolds with lower PVA molecular weight. Our research suggests that the fabricated TE-loaded PVA electrospun dressings represent potential delivery systems of TE for wound care applications.


Assuntos
Betula/química , Nanofibras/química , Triterpenos/farmacologia , Cicatrização/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Peso Molecular , Compostos Orgânicos/química , Compostos Orgânicos/farmacologia , Casca de Planta/química , Álcool de Polivinil/química , Triterpenos/química
10.
Klin Monbl Augenheilkd ; 236(1): 69-73, 2019 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-28514816

RESUMO

Silicone oil endotamponades need to be injected and removed in a reasonable time and under moderate pressure conditions. However, due to ever-decreasing sizes of incisions and trocars, injection and removal of highly viscous silicone oils is very time-consuming. To address resulting problems like longer treatment times or hypotony, thixotropic silicone oils were developed. These oils are characterized by a diminished viscosity under constant mechanical stress; whilst there is pressure or vacuum acting on it, the oils will become more fluid and, therefore, much easier to be applied. Once the force is being removed from the oil, it will automatically return to its initial viscosity after a short time.


Assuntos
Tamponamento Interno , Descolamento Retiniano , Óleos de Silicone , Humanos , Descolamento Retiniano/terapia , Viscosidade , Vitrectomia
11.
Chem Biodivers ; 14(8)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28557380

RESUMO

Seeds of Hypericum perforatum and H. tetrapterum were extracted with dichloromethane and methanol and investigated by chromatographic and mass spectrometric methods. Both species yielded a fatty oil fraction amounting to 30.5% and 18.0% of the seed weight, respectively. Linoleic acid (C18:2n-6) was shown to be the predominant fatty acid constituent. Moreover, xanthone derivatives, i.e. tetrahydroxyxanthones (THX), xanthone-glycosides and xanthone-sulfonates, were assigned in methanolic extracts. For structure elucidation, one representative xanthone, namely 1,3,6,7-THX, was synthesized and analyzed via HPLC-DAD/MSn and GC/MS. Total THX contents were quantitated applying a validated HPLC-DAD method, resulting in 1.25 g/kg (H. perforatum) and 0.27 g/kg (H. tetrapterum), respectively. Moreover, the free radical scavenging capacity of the methanol extracts was tested using the DPPH antioxidant assay. Both, H. perforatum (IC50 = 8.7 mg/l) and 1,3,6,7-THX (IC50 = 3.0 mg/l), exhibited good DPPH free radical scavenging activity compared to Trolox (IC50 = 6.6 mg/l).


Assuntos
Hypericum/química , Lipídeos/química , Lipídeos/farmacologia , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Hypericum/metabolismo , Lipídeos/análise , Espectroscopia de Ressonância Magnética , Oxirredução/efeitos dos fármacos , Fenóis/análise , Sementes/química , Sementes/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Xantonas/análise , Xantonas/química , Xantonas/farmacologia
12.
Pharm Dev Technol ; 22(4): 487-491, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26754018

RESUMO

Skin diseases are usually treated using topical formulations. Frequently, multiple applications per day are necessary, as up to 90% of the formulation (and thus of the active) are withdrawn from the skin by contact with the environment. During the development of topical formulations ex vivo permeation and penetration experiments are deployed to characterize the formulations. Still, these tests do not take into account the removal of formulations during the application period. To date, only few methods exist to probe the substantivity of dermal formulations. The aim of this investigation was to develop methods that simulate skin-to-skin or clothing-to-skin contact and enable the determination of the amount of formulation that is removed from the skin due to the contact. Three different types of formulations were used to validate the systems: a conventional semisolid cream, an oil-in-oil-emulsion, and a film forming formulation. The results showed that the substantivity decreased in the order: film forming formulation > semisolid cream > oil-in-oil-emulsion. A similar trend could be determined with both methods although the total amounts of withdrawn formulation differed. The developed methods can add to the knowledge about the formulation and can be used to develop formulations that exhibit higher substantivity.


Assuntos
Capsaicina/análogos & derivados , Preparações de Ação Retardada/química , Emulsões/química , Óleos/química , Fármacos do Sistema Sensorial/administração & dosagem , Absorção Cutânea , Creme para a Pele/química , Administração Cutânea , Animais , Capsaicina/administração & dosagem , Capsaicina/farmacocinética , Composição de Medicamentos/métodos , Fármacos do Sistema Sensorial/farmacocinética , Pele/metabolismo , Suínos
13.
Skin Pharmacol Physiol ; 29(5): 250-256, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27632222

RESUMO

Triterpenes of the outer bark of birch are known to improve wound healing. An oleogel with these triterpenes as active principle is approved by the European Medicines Agency. As foams can be applied without touching the skin, they might be an advantageous application form. A comparable wound-healing effect can be expected when the permeation flux of the triterpenes from different types of formulations, namely oleogels, water-in-oil emulsions and water-in-oil foams, is similar. The tested formulations were based on three lipids (medium-chain trigylcerides, sunflower oil and paraffin) which differ in their polarity and solvent power for the triterpenes. Infinite dose permeation experiments were performed using porcine skin which was injured by either tape stripping or skin grafting. The results showed that steady-state permeation flux and lag time depend clearly on the depth of the skin lesion. Moreover, it was substantially affected by the lipid used as basis for the different formulations. In contrast, the different formulation types showed a comparable permeation behaviour leading to the conclusion that all formulation types can be used alike for the treatment of wounds, and the results that have already been obtained with oleogels can be directly translated to the foam with its superior use properties.


Assuntos
Sistemas de Liberação de Medicamentos , Absorção Cutânea , Triterpenos/administração & dosagem , Triterpenos/farmacocinética , Animais , Emulsões , Técnicas In Vitro , Compostos Orgânicos , Parafina/química , Permeabilidade , Óleos de Plantas/química , Pele/lesões , Pele/metabolismo , Óleo de Girassol , Suínos , Triglicerídeos/química , Triterpenos/química , Cicatrização
14.
Pharm Dev Technol ; 21(5): 563-75, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26135231

RESUMO

Topical treatment of skin infections is often limited by drawbacks related to both antimicrobial agents and their vehicles. In addition, considering the growing promotion of natural therapeutic products, our objective was to develop and evaluate naturally-based emulsion system, as prospective topical formulation for skin infections-treatment. Therefore, alkyl polyglucoside surfactants were used for stabilization of a vehicle serving as potential carrier for supercritical CO2-extract of Usnea barbata, lichen with well-documented antimicrobial activity, incorporated using two protocols and three concentrations. Comprehensive physicochemical characterization suggested possible involvement of extract's particles in stabilization of the investigated system. Raman spectral imaging served as the key method in disclosing extract's particles potential to participate in the microstructure of the tested emulsion system via three mechanisms: (1) particle-particle aggregation, (2) adsorption at the oil-water interface and (3) hydrophobic particle-surfactant interactions. Stated extract-vehicle interaction proved to be correlated to the preparation procedure and extract concentration on one hand and to affect the physicochemical and biopharmaceutical features of investigated system, on the other hand. Thereafter, formulation with the best preliminary stability and liberation profile was selected for further efficiency and in vivo skin irritation potential evaluation, implying pertinent in vitro antimicrobial activity against G+ bacteria and overall satisfying preliminary safety profile.


Assuntos
Produtos Biológicos/análise , Cromatografia com Fluido Supercrítico/métodos , Emulsificantes/análise , Glucosídeos/análise , Análise Espectral Raman/métodos , Usnea , Produtos Biológicos/farmacologia , Dióxido de Carbono/química , Emulsificantes/farmacologia , Glucosídeos/farmacologia , Humanos , Técnicas de Cultura de Órgãos , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Adulto Jovem
15.
Drug Dev Ind Pharm ; 40(7): 960-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23688275

RESUMO

CONTEXT: Approaching of pharmaceutical and cosmetic industries in some aspects inevitably influence formulation of topical pharmaceuticals, urging researchers to introduce novel excipients with proven benefits over traditional ones. In that context, alkyl polyglucosides (APG) emerge as prominent natural-origin emulsifiers with numerous favorable features (biodegradability, dermatological acceptability, desirable sensory properties). OBJECTIVE: To evaluate APG-stabilized bases (alone and upon addition of isopropyl alcohol) and their impact on skin performance. A simultaneous in vitro/in vivo skin absorption study was conducted to evaluate whether the tape stripping technique could be recommended as an in vivo tool for skin penetration assessment during formulation optimization process. MATERIALS AND METHODS: After a comprehensive physicochemical characterization, biopharmaceutical properties of APG-bases versus reference ones were assessed through a combined in vitro (release/permeation) and in vivo approach. RESULTS AND DISCUSSION: Physicochemical characterization revealed substantial difference in structural ordering due to the formation of various mesomorphic phases. The enhancer-loaded APG base resulted in significantly higher drug levels at all depths into the stratum corneum, indicating that the selected enhancer along with specific colloidal structure has increased the extent of drug delivery. CONCLUSION: Results recommend the investigated emulsifier for stabilization of topical drug delivery systems, not only for their ability to sustain the addition of isopropyl alcohol which proved to be a valuable enhancer, but also satisfactory skin absorption and tolerability when compared to samples stabilized by conventional emulsifier. Tape stripping proved to be a useful and yet inexpensive tool for in vivo trials, able to discriminate subtle differences in dermal availability.


Assuntos
2-Propanol/química , Composição de Medicamentos/métodos , Emulsificantes/química , Álcoois Graxos/química , Glicolipídeos/química , Pele/metabolismo , Varredura Diferencial de Calorimetria , Diclofenaco/administração & dosagem , Diclofenaco/química , Diclofenaco/farmacocinética , Liberação Controlada de Fármacos , Feminino , Humanos , Técnicas In Vitro , Reologia , Absorção Cutânea , Solubilidade , Termogravimetria
16.
Pharm Dev Technol ; 19(1): 55-64, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23259632

RESUMO

CONTEXT: Alkyl polyglucoside surfactants (APG) remain prominent natural origin stabilizers offering a prospect of combining satisfactory stability with mild dermatological properties and complete biodegradability. OBJECTIVE: With the purpose of adjusting the dose to a patient's needs, dilution of commercial corticosteroid formulations is a practice which may modify efficacy uncontrolledly. The rational of the study was to investigate whether a simple change in ready-to-use bases (co-solvent addition) could address these needs in a more predictive manner. METHODS: Hydrocortisone (HC) delivery from such emulsion systems was comparatively assessed employing two in vivo methods: the established human skin blanching assay versus skin stripping technique. RESULTS: HC permeation data obtained after three dose durations showed better overall performance of the APG-stabilized bases relative to reference ones. Although the solubility study showed that all the assessed active samples retained equal thermodynamic activity, diverse HC permeation/penetration implies the importance of the applied base's colloidal structure and/or changes endured. Isopropyl alcohol (IPA) addition offered faster drug penetration enhancement, while glycerol as a moisturizing agent influenced HC penetration through the increase in skin hydration. CONCLUSION: Although the performed in vivo methods cannot be considered alternative, skin stripping technique proved to be a cost-efficient mode of percutaneous penetration assessment, providing additional information on vehicle-skin interactions.


Assuntos
Anti-Inflamatórios/administração & dosagem , Emulsões/farmacologia , Excipientes/farmacologia , Hidrocortisona/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , 2-Propanol/química , 2-Propanol/farmacologia , Adulto , Anti-Inflamatórios/farmacocinética , Emulsões/química , Excipientes/química , Feminino , Glicerol/química , Glicerol/farmacologia , Humanos , Hidrocortisona/farmacocinética , Pele/efeitos dos fármacos , Pele/metabolismo , Adulto Jovem
17.
J Cell Mol Med ; 17(12): 1566-76, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24034629

RESUMO

Alzheimer's disease (AD) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by ß-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti-inflammatory and neuroregulatory activities. Potential therapeutic effects of Oridonin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a nanostructured emulsion, and was orally administrated or injected. Before, during and following the experimental treatments, behavioural tests were performed with these transgenic mice and their naive littermates. Following relatively short-term treatments of 10 days, brain tissue of mice were removed for immunohistochemical assays. The results indicate that both oral treatment and injection of Oridonin significantly attenuated ß-amyloid deposition, plaque-associated APP expression and microglial activation in brain of transgenic mice. Furthermore, injection of Oridonin-nanoemulsion ameliorated deficits in nesting, an important affiliative behaviour, and in social interaction. Additional in vitro studies indicated that Oridonin effectively attenuated inflammatory reaction of macrophage and microglial cell lines. Our results suggest that Oridonin might be considered a promising therapeutic option for human AD or other neurodegenerative diseases.


Assuntos
Amiloidose/tratamento farmacológico , Amiloidose/patologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/patologia , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/uso terapêutico , Administração Oral , Peptídeos beta-Amiloides/metabolismo , Amiloidose/complicações , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Diterpenos do Tipo Caurano/administração & dosagem , Diterpenos do Tipo Caurano/química , Emulsões , Feminino , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/patologia , Relações Interpessoais , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Nanopartículas/química
18.
Drug Dev Ind Pharm ; 39(1): 77-88, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22339172

RESUMO

OBJECTIVES: The aim of the presented work was to develop Ca-alginate microparticles for oral administration of naproxen reinforced with chitosan oligosaccharide (COS) with a special interest to examine the potential of COS for improvement of microparticles stability in simulated intestinal fluid (SIF). METHOD: Microparticles were prepared according to the two-step procedure using an air-jet device with varying calcium chloride and COS concentration in the gelling medium. All prepared microparticles were subjected to size determination, morphology, surface, and inner structure analysis by scanning electron microscopy (SEM), drug loading (DL) and encapsulation efficiency (EE), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, in vitro swelling, and drug release studies. RESULTS: In general, COS-treated microparticles were spherical in shape but somewhat deformed, exhibiting the surface roughness with the mean particle size less than 350 µm. FT-IR and DSC studies confirmed the formation of polyelectrolyte complex (PEC) between alginate and COS, whereas chemical properties and crystalline state of naproxen were unaffected by the encapsulation process. Low naproxen solubility in the gelling medium and rapid entrapment resulted in high encapsulation efficiency (>80.0%). The results of swelling studies demonstrated that COS-treated particles were less sensitive to swelling and erosion in SIF in comparison to the nontreated particles. This resulted in prolonged drug release in SIF, which was dependent on the COS/alginate ratio. CONCLUSION: The obtained findings proved that COS could be used as an effective cross-linking agent for improvement of Ca-alginate microparticles stability in SIF, allowing prolonged release of the encapsulated drug after oral administration.


Assuntos
Alginatos/química , Anti-Inflamatórios não Esteroides/química , Quitosana/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada/química , Naproxeno/química , Oligossacarídeos/química , Alginatos/administração & dosagem , Análise de Variância , Anti-Inflamatórios não Esteroides/administração & dosagem , Quitosana/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos , Ácido Glucurônico/administração & dosagem , Ácido Glucurônico/química , Ácidos Hexurônicos/administração & dosagem , Ácidos Hexurônicos/química , Concentração de Íons de Hidrogênio , Microesferas , Naproxeno/administração & dosagem , Oligossacarídeos/administração & dosagem , Tamanho da Partícula , Estudos Prospectivos
19.
Pharmaceutics ; 14(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35745785

RESUMO

Foam formulations are safe and effective therapy options for the treatment of chronic skin conditions that require the application of a topical formulation to delicate skin areas, such as scalp psoriasis or seborrheic dermatitis. This study focused on the development of foamable emulsions based on aqueous phospholipid blends. The effects of cosurfactants (nonionic Lauryglucoside (LG); zwitterionic Lauramidopropyl betaine (LAPB)), as well as of oil phases of different polarities, namely paraffin oil (PO), medium-chain triglycerides (MCT) and castor oil (CO), were investigated. The foaming experiments showed that both the type of cosurfactant, as well as the type of oil phase, affects the quality of the resulting foam. Emulsions that were based on a combination of hydrogenated lysophosphatidylcholine (hLPC) and a non-hydrogenated phospholipid, as well as LG as a cosurfactant and MCT as an oil phase, yielded the most satisfactory results. Furthermore, profile analysis tensiometry (PAT), polarization microscopy and laser diffraction analysis were used to characterize the developed formulations. These experiments suggest that the employed phospholipids predominantly stabilize the emulsions, while the cosurfactants are mainly responsible for the formation and stabilization of the foams. However, it appears that both sets of excipients are needed in order to acquire stable emulsions with satisfactory foaming properties.

20.
Pharmaceutics ; 14(9)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36145691

RESUMO

Curcuma longa L. is a traditional medicinal and spice plant containing a variety of lipophilic active substances with promising therapeutic properties. In this work, the solvent properties of supercritical carbon dioxide in a pressure and temperature range of 75-425 bar and 35-75 °C were investigated when Curcuma longa rhizomes were extracted. The three main curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, together with the three main constituents of the essential oil, i.e., ar-turmerone, α-turmerone, and ß-turmerone, were analyzed in the resulting extracts. For statistical evaluation, experiments were performed employing a full factorial design, in which flow rate, extraction time, and drug load were kept constant. Within the given conditions, the experimental design revealed an optimum yield of all aforementioned substances, when supercritical carbon dioxide extraction was performed at 425 bar and 75 °C. For comparison, solvent extracts using methanol and n-hexane were prepared and their main components were characterized using LC-MS. The stability of the extracts was monitored upon storage for 6 months at 22 and 40 °C under protection from light. The decomposition of individual compounds was mainly observed in the presence of residual water in the extracts.

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