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1.
Int J Pharm Compd ; 25(2): 146-155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33798114

RESUMO

Recently, there has been an increase in the use of compounded topical pain preparations, raising concerns that clinicians and patients may not be aware of the potential safety risks. Topical diclofenac is one of the most widely used pain medications, often used for joint ailments such as osteoarthritis and other musculoskeletal pain. Systemic exposure to diclofenac has a dose-related risk for gastrointestinal, cardiovascular, and renal adverse events, particularly in elderly patients. Topical diclofenac preparations are frequently compounded in pharmacies at the concentrations of 1% to 10% (or higher) with or without other active ingredients such as camphor. Considering the significantly higher strengths of the compounded preparations as compared to the commercially available products (1% to 3%) and the frequency of application (sometimes up to six times a day), concerns arise as to the levels of absorption with these formulations and their potential toxicity. The objective of this initial study was formulated in an attempt to shed light on safety concerns of topical diclofenac preparations. A study was designed to evaluate the in vitro release, irritability, and permeability of three different concentrations of compounded diclofenac gels (1%, 5%, and 10%) in PLO GEL MEDIFLO and VersaPro Gel bases. Using MatTek's EpiDerm system, skin irritability and the in vitro permeation of compounded diclofenac gels were evaluated. Additionally, the in vitro release profile, drug content, content uniformity, and physical properties of the compounded gels (pH, homogeneity) were assessed. In all cases, the drug content, content uniformity, physical properties, and preparation stability during the recommended beyond-use dating (90 days) were acceptable. The release profiles of all tested preparations followed the Higuchi model. The in vitro skin irritation evaluation of the tested formulations indicated no irritant preparation. The permeability assessment of the formulated gels revealed that there is a correlation between drug release and percutaneous absorption. VersaPro Gelbased preparations, which showed a lower percentage of drug release over the experiment time, showed a significantly lower average flux at steady-state and the average percentage of absorbed dose after 24 hours. The percentage absorption (%abs) from different formulations ranged from 11.18% to 19.6% depending on the gel base. The permeability coefficient, kp, (cm/hr) ranged from 0.019 to 0.037, and the average flux (µg/cm2/hr) ranged from 8.7 to 103 depending on the gel base and the diclofenac concentration. Based on our findings and previously reported data, the possibility exists that higher diclofenac concentrations in compounded topical preparations may lead to significantly higher blood concentrations as compared to commercially available products, which in turn may also lead to serious side effects. Accordingly, there is a need for clinical studies to evaluate the safety of compounded diclofenac preparations with higher diclofenac contents than United States Food and Drug Administrationapproved formulations.


Assuntos
Diclofenaco , Absorção Cutânea , Administração Tópica , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/efeitos adversos , Géis/metabolismo , Humanos , Permeabilidade , Pele/metabolismo
2.
AAPS PharmSciTech ; 22(3): 104, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33718986

RESUMO

Pain is a phenomenon present in the majority of the population, affecting, among others, the elderly, overweight people, and especially recently operated patients, analgesia being necessary. In the specific case of relief of postoperative pain, different kinds of anesthetics are being used, among them bupivacaine, a widely used drug which promotes long-lasting analgesic effects. However, cardiotoxicity and neurotoxicity are related to its repetitive use. To overcome these shortcomings, Novabupi® (a racemic mixture) was developed and is marketed as an injectable solution. This formulation contains an enantiomeric excess of the levogyre isomer, which has reduced toxicity effects. Seeking to rationalize its use by extending the duration of effect and reducing the number of applications, the objectives of this work were to develop and evaluate liposomes containing Novabupi (LBPV), followed by incorporation into thermogel. Liposomes were prepared using the lipid hydration method, followed by size reduction using sonication, and the developed formulations were characterized by hydrodynamic diameter, polydispersity index (PDI), surface zeta potential, and encapsulation efficiency. The selected optimal liposomal formulation was successfully incorporated into a thermogel without loss of thermoresponsive properties, being suitable for administration as a subcutaneous injection. In the ex vivo permeation studies with fresh rodent skin, the thermogel with liposomes loaded with 0.5% LBPV (T-gel formulation 3) showed higher permeation rates compared to the starting formulation, thermogel with 0.5% LBPV (T-Gel 1), which will probably translate into better therapeutic benefits for treatment of postoperative analgesia, especially with regard to the number of doses applied.


Assuntos
Analgesia/métodos , Levobupivacaína/administração & dosagem , Levobupivacaína/farmacocinética , Dor/tratamento farmacológico , Dor/metabolismo , Animais , Bovinos , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/metabolismo , Géis , Humanos , Lipossomos , Masculino , Camundongos , Células NIH 3T3 , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia
3.
Int J Nanomedicine ; 16: 1457-1472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654396

RESUMO

Purpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity. Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model. Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity. Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.


Assuntos
Diflunisal/administração & dosagem , Sistemas de Liberação de Medicamentos , Emulsões/química , Nanogéis/química , Polietilenoglicóis/química , Polietilenoimina/química , Administração Tópica , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Diflunisal/química , Diflunisal/farmacologia , Diflunisal/uso terapêutico , Modelos Animais de Doenças , Composição de Medicamentos , Liberação Controlada de Fármacos , Edema/tratamento farmacológico , Edema/patologia , Condutividade Elétrica , Concentração de Íons de Hidrogênio , Masculino , Tamanho da Partícula , Permeabilidade , Transição de Fase , Ratos , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Solubilidade , Tensoativos/química , Viscosidade
4.
Zhongguo Zhong Yao Za Zhi ; 46(2): 359-365, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645122

RESUMO

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.


Assuntos
Óleos Voláteis , Sesquiterpenos , Humanos , Monoterpenos/metabolismo , Óleos Voláteis/metabolismo , Óleos Voláteis/toxicidade , Sesquiterpenos/metabolismo , Pele/metabolismo , Absorção Cutânea
5.
Int J Nanomedicine ; 16: 1207-1220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33623383

RESUMO

Introduction: The current work aimed to formulate a novel chitosan-based finasteride nanosystem (FNS-NS) for skin delivery to optimize the drug availability in skin for a longer time and enhance ex vivo performance of finasteride against androgenic alopecia. Methods: Both undecorated and chitosan decorated FNS-NSs were synthesized by a high energy emulsification technique. All the prepared nanosystems were further subjected to physicochemical characterizations like pH, viscosity, encapsulation efficiency, surface morphology and in vitro drug release behavior. The influence of the nanosystem on the drug permeation and retention in rat skin was examined using Franz diffusion cell apparatus. Results: The droplet size of developed nanosystems ranged from 41 to 864 nm with a low polydispersity index. The zeta potential of the nanosystems was between -10 mV and +56 mV. This chitosan decorated nanosystem exhibited controlled drug release, ie about 78-97% in 24 h. Among all the nanosystems, our chitosan decorated formulation (F5) had low drug permeation (16.35 µg/cm2) and higher drug retention (10.81 µg/cm2). Conclusion: The abovementioned results demonstrate satisfactory in vitro drug release, skin retention profiles and ex vivo performance with chitosan decorated FNS-NS (F5). This optimized formulation could increase drug availability in skin and could become a promising carrier for topical delivery to treat androgenic alopecia.


Assuntos
Fenômenos Químicos , Sistemas de Liberação de Medicamentos , Finasterida/administração & dosagem , Nanopartículas/química , Administração Cutânea , Animais , Quitosana/química , Liberação Controlada de Fármacos , Finasterida/farmacologia , Cinética , Masculino , Nanopartículas/ultraestrutura , Óleos/química , Permeabilidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Solubilidade , Termodinâmica
6.
Int J Nanomedicine ; 16: 591-607, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33531803

RESUMO

Purpose: The aim of the present study was to develop deflazacort (DFZ) ultra-elastic nanovesicles (UENVs) loaded gel for topical administration to evade gastrointestinal adverse impacts accompanying DFZ oral therapy. Methods: UENVs were elaborated according to D-optimal mixture design employing different edge activators as Span-60, Tween-85 and sodium cholate which were incorporated into the nanovesicles to improve the deformability of vesicles bilayer. DFZ-UENVs were formulated by thin-film hydration technique followed by characterization for different parameters including entrapment efficiency (%EE), particle size, in vitro release and ex vivo permeation studies. The composition of the optimized DFZ-UENV formulation was found to be DFZ (10 mg), Span-60 (30 mg), Tween-85 (30 mg), sodium cholate (3.93 mg), L-α phosphatidylcholine (60 mg) and cholesterol (30 mg). The optimum formulation was incorporated into hydrogel base then characterized in terms of physical parameters, in vitro drug release, ex vivo permeation study and pharmacodynamics evaluation. Finally, pharmacokinetic study in rabbits was performed via transdermal application of UENVs gel in comparison to oral drug. Results: The optimum UENVs formulation exhibited %EE of 74.77±1.33, vesicle diameter of 219.64±2.52 nm, 68.88±1.64% of DFZ released after 12 h and zeta potential of -55.57±1.04 mV. The current work divulged successful augmentation of the bioavailability of DFZ optimum formulation by about 1.37-fold and drug release retardation compared to oral drug tablets besides significant depression of edema, cellular inflammation and capillary congestion in carrageenan-induced rat paw edema model. Conclusion: The transdermal DFZ-UENVs can achieve boosted bioavailability and may be suggested as an auspicious non-invasive alternative platform for oral route.


Assuntos
Anti-Inflamatórios/farmacologia , Sistemas de Liberação de Medicamentos , Elasticidade , Nanopartículas/química , Pregnenodionas/farmacologia , Administração Cutânea , Administração Oral , Animais , Disponibilidade Biológica , Liberação Controlada de Fármacos , Edema/tratamento farmacológico , Hidrogéis/química , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Pregnenodionas/farmacocinética , Coelhos , Ratos Wistar , Absorção Cutânea/efeitos dos fármacos , Eletricidade Estática , Comprimidos
7.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540792

RESUMO

The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium. Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function. We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress. Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment. Blood parameters indicated primary and secondary stress responses at both sampling points. At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01). Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin. Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures. Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress. Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.


Assuntos
Aglomeração , Mucinas/metabolismo , Muco/química , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Salmo salar/metabolismo , Absorção Cutânea/fisiologia , Pele/metabolismo , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Animais , Biomarcadores , Cromatografia Líquida , Aglomeração/psicologia , Glicosilação , Hidrocortisona/sangue , Manitol/farmacocinética , Espectrometria de Massas , Mucinas/isolamento & purificação , Muco/metabolismo , Ácido N-Acetilneuramínico/isolamento & purificação , Oxigênio/análise , Polissacarídeos/isolamento & purificação , Processamento de Proteína Pós-Traducional , Salmo salar/sangue , Pele/ultraestrutura , Temperatura , Qualidade da Água
8.
Int J Nanomedicine ; 16: 119-132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33447031

RESUMO

Purpose: This manuscript aimed at encapsulating an antifungal terconazole (TCZ) into innovative novasomes for improving its penetration into the skin and clinically modulating its therapeutic efficacy. Methods: Novasomes containing free fatty acid (FFA) as a penetration enhancer were formulated using ethanol injection technique based on 24 full factorial design to explore the impact of various formulation variables on novasomes characteristics regarding entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formulation was chosen using Design-Expert® software and utilized for further explorations. Results: The chosen formulation (N15; including 100 mg lipid components and Span 80 to oleic acid in a ratio of 2:1 (w/w)) exhibited an EE% = 99.45 ± 0.78%, PS = 623.00 ± 2.97 nm, PDI = 0.40 ± 0.04, and ZP = -73.85 ± 0.64 mV. N15 showed spherical vesicles with a higher deformability index (DI) (9.62 ± 0.15 g) compared to traditional niosomal formulation (0.92 ± 0.12 g). Further, N15 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis-(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition tests revealed a superior TCZ deposition inside the skin from N15 in comparison to traditional niosomal formulation and TCZ suspension. Furthermore, histopathological examination for rats assured the safety of N15 for topical use. A clinical study conducted on infants suffering from napkin candidiasis proved the superiority of N15 to placebo in providing a complete cure of such fungal infections. Conclusion: Concisely, the obtained outcomes confirmed the pronounced efficacy of N15 to successfully treat skin fungal infections.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Triazóis/administração & dosagem , Administração Tópica , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Análise Fatorial , Humanos , Lactente , Lipossomos , Masculino , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Eletricidade Estática , Suspensões , Triazóis/farmacologia , Triazóis/uso terapêutico
9.
Int J Nanomedicine ; 16: 133-145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33447032

RESUMO

Background: Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes. Aim: The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses. Methodology: To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-α, NF-кB and COX-2 were assessed in paw tissue before and after treatment. Results: The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 ± 3.6 nm, and 83.6 ± 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 ± 0.25 µg/cm2/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 ± 0.12 µg/cm2/hr and 0.64 ± 0.09 µg/cm2/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-α, NF-кB and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel. Conclusion: The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Celecoxib/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , NF-kappa B/metabolismo , Nanopartículas/química , Fator de Necrose Tumoral alfa/metabolismo , Administração Cutânea , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/genética , Celecoxib/farmacologia , Ciclo-Oxigenase 2/genética , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Adjuvante de Freund , Regulação da Expressão Gênica/efeitos dos fármacos , Cinética , Lipossomos , Masculino , Camundongos , NF-kappa B/genética , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Reologia , Absorção Cutânea/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
10.
Molecules ; 26(2)2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435259

RESUMO

Epilobium angustifolium L. is applied as an antiseptic agent in the treatment of skin diseases. However, there is a lack of information on human skin penetration of active ingredients with antioxidative potential. It seems crucial because bacterial infections of skin and subcutaneous tissue are common and partly depend on oxidative stress. Therefore, we evaluated in vitro human skin penetration of fireweed ethanol-water extracts (FEEs) by determining antioxidant activity of these extracts before and after penetration study using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and Folin-Ciocalteu methods. Microbiological tests of extracts were done. The qualitative and quantitative evaluation was performed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC-UV) methods. The in vitro human skin penetration using the Franz diffusion chamber was assessed. The high antioxidant activity of FEEs was found. Gallic acid (GA), chlorogenic acid (ChA), 3,4-dihydroxybenzoic acid (3,4-DHB), 4-hydroxybenzoic acid (4-HB), and caffeic acid (CA) were identified in the extracts. The antibacterial activities were found against Serratia lutea, S. marcescens, Bacillus subtilis, B. pseudomycoides, and B. thuringiensis and next Enterococcus faecalis, E. faecium, Streptococcus pneumoniae, Pseudomonas aeruginosa, and P. fluorescens strains. In vitro penetration studies showed the penetration of some phenolic acids and their accumulation in the skin. Our results confirm the importance of skin penetration studies to guarantee the efficacy of formulations containing E. angustifolium extracts.


Assuntos
Anti-Infecciosos , Antioxidantes , Bactérias/crescimento & desenvolvimento , Bassia scoparia/química , Extratos Vegetais , Absorção Cutânea , Pele/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Etanol/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Pele/microbiologia , Água/química
11.
ACS Appl Mater Interfaces ; 13(2): 2382-2398, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33406837

RESUMO

In this article, we describe a method of delivery of chondroitin sulfate to skin as nanoparticles and demonstrate its anti-inflammatory and antioxidant role using UV irradiation as a model condition. These nanoparticles, formed through electrostatic interactions of chondroitin sulfate with a skin-penetrating peptide, were found to be homogenous with positive surface charges and stable at physiological and acidic pH under certain conditions. They were able to enter into the human keratinocyte cell line (HaCaT), artificial skin membrane (mimicking the human skin), and mouse skin tissue unlike free chondroitin sulfate. The preapplication of nanoparticles also exhibited reduced levels of oxidative stress, cyclobutane pyrimidine dimer formation, TNF-α, and so on in UV-B-irradiated HaCaT cells. In an acute UV-B irradiation mouse model, their topical application resulted in reduced epidermal thickness and sunburn cells, unlike in the case of free chondroitin sulfate. Thus, a completely noninvasive method was used to deliver a bio-macromolecule into the skin without using injections or abrasive procedures.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Portadores de Fármacos/química , Peptídeos/química , Queimadura Solar/prevenção & controle , Administração Tópica , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Linhagem Celular , Sulfatos de Condroitina/farmacocinética , Sulfatos de Condroitina/uso terapêutico , Portadores de Fármacos/metabolismo , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/metabolismo , Absorção Cutânea , Queimadura Solar/metabolismo , Queimadura Solar/patologia , Raios Ultravioleta/efeitos adversos
12.
Int J Pharm ; 595: 120242, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33484919

RESUMO

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-ß1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.


Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Plasma Rico em Plaquetas/metabolismo , Envelhecimento da Pele/efeitos da radiação , Dermatopatias/terapia , Pele/efeitos da radiação , Infecções Cutâneas Estafilocócicas/terapia , Administração Cutânea , Animais , Terapia Combinada , Citocinas/farmacocinética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacocinética , Lasers de Gás/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos , Suínos , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação
13.
Ann Work Expo Health ; 65(2): 206-218, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33313651

RESUMO

OBJECTIVES: Bisphenol A (BPA) is the most used colour developer in thermal paper for cashiers receipts, labels, and tickets. BPA can migrate onto the skin and be absorbed when handling these papers. BPA is a known endocrine disruptor and is therefore being replaced in thermal paper by some alternatives such as Bisphenol S (BPS), D-8, and Pergafast 201® (PF201). To our knowledge, no studies have characterized skin permeation of these BPA alternatives. METHODS: We measured/characterized skin absorption for BPA, BPS, D-8, and PF201 through ex vivo human skin using flow-through diffusion cells according to OECD guideline 428. Skin samples were 7-12 per test substance from three different skin donors. Skin metabolism was studied for BPA. Dermal absorption was expressed as the amount of the BPA alternatives in the receptor fluid over applied dose in percent (%). RESULTS: The absorbed dose after 24 h of exposure was 25% for BPA, 17% for D-8, 0.4% for BPS, and D-8 >> BPS > PF201. These results are in agreement with their log Kow and molecular weights. We provided here the necessary data to estimate the extent of skin absorption of BPA analogues, which is a necessary step in risk assessment, and ultimately evaluate public health risks posed by D-8, BPS, and PF201.


Assuntos
Exposição Ocupacional , Absorção Cutânea , Compostos Benzidrílicos , Humanos , Exposição Ocupacional/análise , Papel , Fenóis , Pele
14.
Carbohydr Polym ; 252: 117132, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183591

RESUMO

Transdermal immunomodulation is of increasing interest as an efficient drug delivery method. It non-invasively delivers drugs directly to skin-resident immune cells, thereby avoiding the first-pass metabolism. Herein, we prepared ovalbumin-conjugated hyaluronic acid-methacrylate (HAMA-OVA) and schizophyllan-methacrylate (SPGMA) hybrid nanogels and investigated their suitability for topical delivery. The particle size was controlled to between 100 and 300 nm using ultrasonication and filtering processes. The nanogels penetrated the porcine stratum corneum layer and were deposited in the dermis via hybridization with HAMA. In addition, the hybridized SPGMA promoted the internalization of the nanogels into dendritic cells (DCs; JAWSII), which resulted in an improvement in the ovalbumin delivery efficiency. In molecular biological assessments, the hybrid nanogels upregulated the DC activation marker interleukin-6 and induced DC maturation, indicating antigen-presenting behavior. These results suggest that HAMA/SPGMA hybrid nanogels are a promising topical delivery carrier for immunomodulation and vaccinations.


Assuntos
Células Dendríticas/efeitos dos fármacos , Portadores de Fármacos/química , Nanogéis/química , Administração Cutânea , Animais , Linhagem Celular , Ácido Hialurônico/química , Fatores Imunológicos/química , Imunomodulação , Metacrilatos/química , Camundongos , Ovalbumina/química , Estudo de Prova de Conceito , Sizofirano/química , Absorção Cutânea , Suínos , beta-Glucanas/química
15.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5193-5199, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350235

RESUMO

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.


Assuntos
Glycyrrhiza , Administração Cutânea , Animais , Liberação Controlada de Fármacos , Emulsões , Géis , Camundongos , Absorção Cutânea
16.
Int J Nanomedicine ; 15: 7627-7650, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116492

RESUMO

The skin is the largest organ in the human body, providing a barrier to the external environment. It is composed of three layers: epidermis, dermis and hypodermis. The most external epidermis is exposed to stress factors that may lead to skin conditions such as photo-aging and skin cancer. Some treatments for skin disease utilize the incorporation of drugs or bioactive compounds into nanocarriers known as liposomes. Liposomes are membranes whose sizes range from nano to micrometers and are composed mostly of phospholipids and cholesterol, forming similar structures to cell membranes. Thus, skin treatments with liposomes have lower toxicity in comparison to traditional treatment routes such as parenteral and oral. Furthermore, addition of edge activators to the liposomes decreases the rigidity of the bilayer structure making it deformable, thereby improving skin permeability. Liposomes are composed of an aqueous core and a lipidic bilayer, which confers their amphiphilic property. Thus, they can carry hydrophobic and hydrophilic compounds, even simultaneously. Current applications of these nanocarriers are mainly in the cosmetic and pharmaceutic industries. Nevertheless, new research has revealed promising results regarding the effectiveness of liposomes for transporting bioactive compounds through the skin. Liposomes have been well studied; however, additional research is needed on the efficacy of liposomes loaded with bioactive peptides for skin delivery. The objective of this review is to provide an up-to-date description of existing techniques for the development of liposomes and their use as transporters of bioactive compounds in skin conditions such as melanoma and skin inflammation. Furthermore, to gain an understanding of the behavior of liposomes during the process of skin delivery of bioactive compounds into skin cells.


Assuntos
Inflamação/patologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Pele/patologia , Transporte Biológico , Humanos , Lipossomos/ultraestrutura , Absorção Cutânea
17.
Pharm Res ; 37(10): 195, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32944793

RESUMO

PURPOSE: Design imiquimod-loaded chitosan nanocapsules for transdermal delivery and evaluate the depth of imiquimod transdermal absorption as well as the kinetics of this absorption using Raman Microscopy, an innovative strategy to evaluate transdermal absorption. This nanovehicle included Compritol 888ATO®, a novel excipient for formulating nanosystems whose administration through the skin has not been studied until now. METHODS: Nanocapsules were made by solvent displacement method and their physicochemical properties was measured by DLS and laser-Doppler. For transdermal experiments, newborn pig skin was used. The Raman spectra were obtained using a laser excitation source at 532 nm and a 20/50X oil immersion objective. RESULTS: The designed nanocapsules, presented nanometric size (180 nm), a polydispersity index <0.2 and a zeta potential +17. The controlled release effect of Compritol was observed, with the finding that half of the drug was released at 24 h in comparison with control (p < 0.05). It was verified through Raman microscopy that imiquimod transdermal penetration is dynamic, the nanocapsules take around 50 min to penetrate the stratum corneum and 24 h after transdermal administration, the drug was in the inner layers of the skin. CONCLUSIONS: This study demonstrated the utility of Raman Microscopy to evaluate the drugs transdermal penetration of in the different layers of the skin. Graphical Abstract New imiquimod nanocapsules: evaluation of their skin absorption by Raman Microscopy and effect of the compritol 888ATO® in the imiquimod release profile.


Assuntos
Quitosana/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Ácidos Graxos/farmacocinética , Imiquimode/farmacocinética , Nanocápsulas/administração & dosagem , Pele/metabolismo , Administração Cutânea , Animais , Quitosana/administração & dosagem , Quitosana/química , Ácidos Graxos/administração & dosagem , Ácidos Graxos/química , Imiquimode/administração & dosagem , Imiquimode/química , Nanocápsulas/química , Microscopia Óptica não Linear/métodos , Absorção Cutânea , Suínos
18.
J Oleo Sci ; 69(10): 1307-1315, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32908096

RESUMO

Ceramide, an intercellular lipid of the stratum corneum, plays an essential role in making the skin barrier. One problem with the use of medical adhesive tape or sheets for skin is that their repeated attachment and detachment may cause some damage to the skin. An attempt has been made to eliminate this problem by mixing ceramide into the adhesive of sheets, and has delivered excellent clinical results. This study aimed to investigate whether ceramide is transferred from the adhesive with added ceramide to the skin. An adhesive sheet was prepared by adding synthetic ceramide (CER) to UV-curable acrylic adhesive gel. After affixing the adhesive sheet to human skin for a certain period, it was peeled off and cut perpendicular to the adhesive surface. Synchrotron micro-infrared spectroscopy of the sectioned samples showed that the ceramide concentration in the gel sheet decreases as the application time to human skin increases. This is thought to be due to the release of CER from the gel sheet.


Assuntos
Adesivos , Ceramidas/administração & dosagem , Ceramidas/metabolismo , Liberação Controlada de Fármacos , Absorção Cutânea , Pele/metabolismo , Fita Cirúrgica , Ceramidas/análise , Géis , Humanos , Espectrofotometria Infravermelho
19.
Int J Nanomedicine ; 15: 6007-6018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884260

RESUMO

Background: Skin pharmacokinetics is an indispensable indication for studying the drug fate after administration of transdermal drug delivery systems (TDDS). However, the heterogeneity and complex skin structured with stratum corneum, viable epidermis, dermis, and subcutaneous tissue inevitably leads the drug diffusion coefficient (Kp) to vary depending on the skin depth, which seriously limits the development of TDDS pharmacokinetics in full thickness skin. Methods: A multilayer geometry skin model was established and the Kp of drug in SC, viable epidermis, and dermis was obtained using the technologies of molecular dynamics simulation, in vitro permeation experiments, and in vivo microdialysis, respectively. Besides, finite element analysis (FEA) based on drug Kps in different skin layers was applied to simulate the paeonol nanoemulsion (PAE-NEs) percutaneous dynamic penetration process in two and three dimensions. In addition, PAE-NEs skin pharmacokinetics profile obtained by the simulation was verified by in vivo experiment. Results: Coarse-grained modeling of molecular dynamic simulation was successfully established and the Kp of PAE in SC was 2.00×10-6 cm2/h. The Kp of PAE-NE in viable epidermis and in dermis detected using penetration test and microdialysis probe technology, was 1.58×10-5 cm2/h and 3.20×10-5 cm2/h, respectively. In addition, the results of verification indicated that PAE-NEs skin pharmacokinetics profile obtained by the simulation was consistent with that by in vivo experiment. Discussion: This study demonstrated that the FEA combined with the established multilayer geometry skin model could accurately predict the skin pharmacokinetics of TDDS.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Emulsões/farmacocinética , Epiderme/efeitos dos fármacos , Nanoestruturas/administração & dosagem , Acetofenonas/administração & dosagem , Acetofenonas/farmacocinética , Animais , Emulsões/administração & dosagem , Células Epidérmicas/efeitos dos fármacos , Análise de Elementos Finitos , Masculino , Microdiálise , Modelos Biológicos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos
20.
Yakugaku Zasshi ; 140(9): 1175-1183, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879249

RESUMO

The mock patches were prepared with novel acrylic polymers as adhesive layer where biphenyl-4-ylacetic acid (BAA) or 2-(2-fluorobiphenyl-4-yl) propanoic acid (FPA) was used as model active pharmaceutical ingredients (APIs). In addition, the mock patches were formulated with typical ester ingredients for transdermal dosage forms. The molecular state of the model APIs in the adhesive layer was observed by polarized microscope and microscopic Raman spectroscopy, which contains both conventional and low frequency (LF) region. Crystallization behavior would be depended on the interaction between API and polymers in the adhesive layer. In particular, LF Raman measurement was useful to discriminate API polymorphs. The pharmaceutical properties including dissolution and skin permeation of APIs were also evaluated for mock patches. The drug release and transdermal permeation were enhanced with the ester ingredients such as isopropyl myristate and diethyl sebacate due to their diffusion to the test solution or the skin stratum corneum as well as reducing the interaction between API and polymers. Further, the tack strength was not changed, but the peel strength was weakened by the additives. Thus, the adhesive properties were controllable by formulation with the additives. These findings could enable to evaluate the interaction between API and the polymers for adhesive layer and select the appropriate polymer and additives for used APIs when designing the drug products.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Polímeros , Adesivo Transdérmico , Adesividade , Administração Cutânea , Ácidos Decanoicos , Liberação Controlada de Fármacos , Miristatos , Fenilacetatos/administração & dosagem , Fenilacetatos/metabolismo , Propionatos/administração & dosagem , Propionatos/metabolismo , Absorção Cutânea , Solubilidade , Análise Espectral Raman
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