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1.
Environ Monit Assess ; 192(3): 157, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016621

RESUMO

Quantitatively characterizing dermal exposure for workers and consumers performing tasks with hand-applied cleaning solution is complex as many of the assessment variables are scenario specific. One of the key variables necessary for quantitatively estimating dermal exposure is the surface area of the hand contacted by the cleaning solution. However, no relevant data or methods are available in the literature. This study evaluated the feasibility of a novel simulation approach to measure skin contact area specific to hand cleaning with various types of liquid cleaning products to refine exposure and risk estimates for users of these products. This approach incorporates cotton rags wetted with pigmented cleaning solutions, volunteers wearing white cotton gloves during hand cleaning with those cotton rags, and digital imaging of the pigmented solution-contacted gloves post-simulation to quantify area of the hand contacted by the cleaning solution. When applied across three separate cleaning solutions, a denatured alcohol, an aqueous solution, and a lacquer thinner, this novel method performed well in estimating both palmer and dorsal surface areas of the hand contacted during simulated cleaning. The volume of cleaning solution applied to the rag and thickness of the rag were consistent predictors of contacted surface area. For the denatured alcohol, the time spent cleaning was additionally correlated with contacted surface area. This study suggests that this novel simulation approach could be an important tool for reducing an important source of uncertainty in dermal exposure assessments involving hand-applied cleaning solutions.


Assuntos
Detergentes , Monitoramento Ambiental , Exposição Ocupacional , Absorção Cutânea , Mãos , Humanos , Pele
3.
JAMA ; 323(3): 256-267, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31961417

RESUMO

Importance: A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA). Objective: To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions. Design, Setting, and Participants: Randomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019. Interventions: Participants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant. Main Outcomes and Measures: The primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21. Results: Among 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants. Conclusions and Relevance: In this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen. Trial Registration: ClinicalTrials.gov Identifier: NCT03582215.


Assuntos
Propiofenonas/sangue , Absorção Cutânea , Protetores Solares/farmacocinética , Acrilatos/sangue , Acrilatos/farmacocinética , Adulto , Benzofenonas/sangue , Benzofenonas/farmacocinética , Cinamatos/sangue , Cinamatos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propiofenonas/farmacocinética , Salicilatos/sangue , Salicilatos/farmacocinética , Protetores Solares/efeitos adversos
4.
Toxicol Lett ; 319: 237-241, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31738974

RESUMO

The RSDL® (Reactive Skin Decontamination Lotion) Kit contains a lotion-impregnated sponge extensively studied for the removal or neutralization of chemical warfare agents from skin. Pilot investigation of efficacy with industrial threat compounds noted that synthetic opioid fentanyl citrate was removed by the RSDL Kit but not chemically inactivated by the lotion. This implies that after use the RSDL Kit will contain intact fentanyl, which may pose a dermal health hazard if the fentanyl is then transferred to skin after use without proper handling. This in vitro investigation studied the contaminated RSDL Kit using three different concentrations of fentanyl with a skin contact time of 15 min under direct interaction from passive contact, light touch, and leaning with one hand. It was demonstrated that the expected transfer of fentanyl from contaminated RSDL depends on 1) the concentration of fentanyl and 2) the area of the exposed surface. From a toxicological perspective, the contact risk of fentanyl under the conditions tested can be considered low but not absent. The present study determined that a contaminated RSDL Kit, used for removal of fentanyl, should be handled with proper care. Use of protective gloves in operational use and washing skin afterwards is advised to prevent undesired contamination.


Assuntos
Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/análise , Contaminação de Medicamentos , Fentanila/efeitos adversos , Fentanila/análise , Creme para a Pele/efeitos adversos , Creme para a Pele/análise , Animais , Substâncias para a Guerra Química/química , Técnicas In Vitro , Projetos Piloto , Medição de Risco , Absorção Cutânea , Suínos
5.
Chemosphere ; 239: 124811, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726522

RESUMO

China has been suffering from endemic fluorosis for the past 30 years. This study investigated fluoride concentrations in 10 districts of Tianjin, China, to illustrate their spatial distribution characteristics and potential human health risks. The results showed fluoride concentration of 0.01-6.30 mg L-1 with a mean value of 0.99 mg L-1, and 78.82% of water fluoride reaches the standard for drinking water (1.5 mg L-1). Higher fluoride levels were recorded in deep well pumps supply zones, and more potential changes in fluoride occurred was positively correlated with pH in groundwater. Mean value of fluoride in drinking water in 10 districts followed the order of WQ > BC > JZ > NH > BD > BH > JN > JH > DL > XQ. Estimations of non-carcinogenic risk for drinking water indicated that mean hazard quotient values of fluoride for combined pathways (i.e., oral ingestion and dermal absorption) were >1.0 for all age groups of WQ and BC. The results also showed that the estimated risk primarily came from the ingestion pathway. Risk levels for children varied obviously, generally in the order of 1-4y > 4-7y > 7-9y (years old). In the central tendency center and reasonable maximum exposure conditions, estimated risks were 1.25, 1.12, 0.771 and 3.66, 3.29, 2.27, respectively. The results supply material information for health authorities in fluorosis areas to put forward more efficient policies to control the endemic diseases. Attention should be paid to the formulation of health promotion strategies and measures to reduce fluoride intake in order to protect the health of residents.


Assuntos
Água Potável/química , Fluoretos/análise , Fluorose Dentária/epidemiologia , Abastecimento de Água , Criança , Pré-Escolar , China/epidemiologia , Ingestão de Alimentos , Água Subterrânea , Humanos , Lactente , Minerais/análise , Probabilidade , Medição de Risco , Absorção Cutânea
6.
Int J Nanomedicine ; 14: 9275-9284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819429

RESUMO

Purpose: Thymosin ß-4(Tß-4) is a macromolecular protein drug with potential for drug development in wound repair but is limited by the shortcomings of macromolecular protein, such as large volumes, poor membrane permeability, and unstable physicochemical characteristics. Ethosomes could enhance cell membrane fluidity and reduce epidermal membrane density to make macromolecular drugs through the stratum corneum into the deeper layers of the skin easily. Herein, we developed and characterized a novel transdermal delivery vehicle to load macromolecular protein peptides and use Tß-4 as a model drug wrapped into ethosomes. Methods: We used the orthogonal method to optimize the formulation of the ethosome preparation prepared by the ethonal infusion method. Ethosomal gels were characterized by using different analytical methods. Transdermal release rate in vitro have been demonstrated in Franz diffusion cells and the efficacy of drug-loaded nanocarriers in vivo was investigated in a mouse model. Results: Optimized Tß-4 ethosomal gels have good physicochemical properties. The drug amounts of the cumulative release in the ethosomal gel within 5 hours were 1.67 times that of the T-ß4 gel in vitro release study, and the wound healing time of ethosomal gel group was only half of the T-ß4 gel group in vivo pharmacokinetic study. Compared with the free drug group, the ethosome preparation not only promotes the percutaneous absorption process of the macromolecular protein drugs but also shortened wound recovery time. Conclusion: Hence, we provide a possible good design for ethosomal gel system that can load macromolecular protein peptide drugs to achieve transdermal drug administration, promoting the percutaneous absorption of the drug and improving the effect.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Etanol/química , Géis/química , Timosina/administração & dosagem , Administração Cutânea , Animais , Liberação Controlada de Fármacos , Feminino , Lipossomos , Camundongos , Tamanho da Partícula , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea , Testes de Irritação da Pele , Timosina/farmacocinética , Cicatrização/efeitos dos fármacos
7.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4627-4633, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872657

RESUMO

This study aimed to investigate the transdermal enhancing effect of essential oil from Zanthoxylum bungeanum(Z. bungeanum oil) in microemulsion gel(ZO-ME-gel) on permeation of different components,and reveal the transdermal enhancing mechanism of ZO-ME-gel. A series of components with different log P values were selected as model drugs and encapsulated in ZO-ME-gel to simplify and characterize the complex components of traditional Chinese medicine. The transdermal behavior of the model drugs was further examined using the improved Franz diffusion cell method. Then attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR),differential scanning calorimetry(DSC) studies and hematoxylin-eosin(HE) staining were used to investigate the effects of Z. bungeanum oil and ZO-ME-gel on keratin,intercellular lipids and microstructure of the stratum corneum(SC). The results showed that Z. bungeanum oil and ZO-ME-gel had a good transdermal enhancing effect on both hydrophilic and lipophilic drugs,and the best effect was achieved when log P value was-0. 5. The transdermal enhancing mechanism of Z. bungeanum oil and ZO-ME-gel was related to affecting the order of the SC lipids,changing lipid fluidity and protein conformation,and disrupting the integrity of the SC structure. 5% Z. bungeanum oil had greater transdermal enhancing effect and destruction of SC structure than ZO-ME-gel. These results suggested that Z. bungeanum oil loaded in microemulsion gel still had a good transdermal enhancing effect although the effect was not as great as Z. bungeanum oil itself,in addition,ZO-ME-gel was less irritating to the skin and safer to use,which had a guiding role in the development and clinical application of Z. bungeanum oil-containing traditional Chinese medicine topical preparations.


Assuntos
Óleos Voláteis , Zanthoxylum , Administração Cutânea , Pele , Absorção Cutânea
8.
Chem Pharm Bull (Tokyo) ; 67(11): 1225-1231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31685750

RESUMO

Solifenacin (Sol), an antimuscarinic agent has been widely used for the treatment of overactive bladder. Transdermal formulations can be administered without water as well as absorbed slowly into the blood over a long period of time. The aim of this study was to develop cream and tape formulations of Sol, and evaluate the transdermal permeation and absorption of the drug from the two formulations in vitro and in vivo, respectively. In the preparation of cream formulation, Sol succinate was dissolved in purified water, and the mixture was added to the hydrophilic cream. Then, aqueous sodium hydroxide was added to the cream. In the tape formulation, Sol succinate was dissolved in a solvent with propylene glycol, diisopropanolamine, triethyl citrate, and EUDRAGIT E100. The dissolved solvent was poured onto a polyethylene film. Cream (5%) and tape (15%) formulations demonstrated high skin permeability. Addition of an adsorption enhancer (N-methyl-2-pyrrolidone) did not further increase the level of skin permeability. In subsequent in vivo experiments in rats, both the cream and tape formulations led to slow absorption of Sol into plasma, with increased t1/2 compared with oral administration. Plasma Sol concentrations peaked 24 h after transdermal application and the drug was still detectable in plasma 72 h after application. Additionally, the cream (5%) and tape (15%) formulations resulted in a higher area under the plasma concentration vs. time curve from 0 to 72 h (AUC0-72) compared with oral formulation (30 mg/kg). In conclusion, significant in vitro permeability and in vivo absorption of Sol from the transdermal formulations were observed.


Assuntos
Pele/metabolismo , Succinato de Solifenacina/metabolismo , Administração Cutânea , Animais , Concentração de Íons de Hidrogênio , Masculino , Permeabilidade , Ratos , Ratos Sprague-Dawley , Pele/química , Absorção Cutânea , Succinato de Solifenacina/administração & dosagem , Succinato de Solifenacina/química , Solubilidade
9.
AAPS PharmSciTech ; 20(8): 330, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677079

RESUMO

The present work attempts to develop and optimize the formula of a lipidic nanoemulsion (NE) containing sodium hyaluronate (HNa) and indomethacin (Ind) as HNa-Ind for enhanced transdermal antiarthritic activity. NEs were prepared by the spontaneous emulsification method and characterized by Fourier-transform infrared (FTIR) spectroscopy. The composition of the optimal formulation was statistically optimized using Box-Behnken experimental design method with three independent factors and was characterized for particle size, polydispersity index, and percent transmittance. The selected formula was tested for its in vitro antioxidant activity and in vivo anti-inflammatory activity. The optimized HNa-Ind NE formula was characterized and displayed a particle size of 12.87 ± 0.032 nm, polydispersity index of 0.606 ± 0.082, and 99.4 ± 0.1 percentage of transmittance. FTIR showed no interaction between HNa and Ind as a physical mixture. In addition, the optimized HNa-Ind NE was able to preserve the antioxidant ability of the two drugs, as evidenced through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assay used to assess free radical scavenging ability. The cell viability was increased while the free radical scavenging activity was decreased (94.28% inhibition at higher concentrations compared with vitamin C as a reference with an inhibition of 100%). Moreover, the pharmacological anti-inflammatory potential of the optimized HNa-Ind NE formulation was assessed using an in vivo model. Compared with reference drugs (ibuprofen gel 5%), the remarkable activity of the optimized formulation was established using xylene-induced ear edema in mice model, in which the inflamed region reduced by 92.5% upon treatment. The optimized HNa-Ind NE formulation showed considerably higher skin permeation and drug deposition capability compared with the HNa-Ind solution. HNa-Ind NE was demonstrated to be a successful carrier with enhanced antioxidant and anti-inflammatory potential while showing better skin penetration, thus being a promising vehicle for transdermal drug delivery.


Assuntos
Desenvolvimento de Medicamentos/métodos , Ácido Hialurônico/síntese química , Indometacina/síntese química , Nanopartículas/química , Administração Cutânea , Animais , Emulsões , Feminino , Indometacina/metabolismo , Lipídeos , Masculino , Camundongos , Nanopartículas/metabolismo , Tamanho da Partícula , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia
10.
Drug Deliv ; 26(1): 1140-1154, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31736366

RESUMO

The current study aimed to encapsulate fluvastatin sodium (FVS), a member of the statins family possessing pleiotropic effects in rheumatoid arthritis (RA), into spanlastic nanovesicles (SNVs) for transdermal delivery. This novel delivery could surmount FVS associated oral encumbrances such as apparent first-pass effect, poor bioavailability and short elimination half-life, hence, accomplishing platform for management of RA. To consummate this objective, FVS-loaded SNVs were elaborated by thin film hydration method, utilizing either Span 60 or Span 80, together with Tween 80 or Brij 35 as an edge activator according to full factorial design (24). Applying Design-Expert® software, the influence of formulation variables on SNVs physicochemical properties and the optimized formulation selection were explored. Additionally, the pharmacokinetic studies were scrutinized in rats. Furthermore, in Freund's adjuvant-induced arthritis, rheumatoid markers, TNF-α, IL-10, p38 MAPK, and antioxidant parameters were measured. The optimum SNVs were nano-scaled spherical vesicles (201.54 ± 9.16 nm), having reasonable entrapment efficiency (71.28 ± 2.05%), appropriate release over 8 h (89.45 ± 3.64%) and adequate permeation characteristics across the skin (402.55 ± 27.48 µg/cm2). The pharmacokinetic study disclosed ameliorated bioavailability of the optimum SNVs gel by 2.79- and 4.59-fold as compared to the oral solution as well as the traditional gel, respectively. Moreover, it elicited a significant suppression of p38 MAPK expression and also significant improvement of all other measured biomarkers. Concisely, the foregoing findings proposed that SNVs can be auspicious for augmenting FVS transdermal delivery for management of RA.


Assuntos
Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Fluvastatina/administração & dosagem , Adjuvante de Freund/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Administração Cutânea , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Tamanho da Partícula , Permeabilidade , Ratos , Ratos Wistar , Absorção Cutânea
11.
BMC Complement Altern Med ; 19(1): 334, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771651

RESUMO

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.


Assuntos
Benzoquinonas , Portadores de Fármacos , Nanomedicina/métodos , Fosfolipídeos , Psoríase , Animais , Benzoquinonas/administração & dosagem , Benzoquinonas/química , Benzoquinonas/farmacocinética , Modelos Animais de Doenças , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Camundongos , Nigella sativa/química , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Fosfolipídeos/farmacologia , Psoríase/metabolismo , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Absorção Cutânea/efeitos dos fármacos
12.
Int J Pharm Compd ; 23(6): 496-503, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751946

RESUMO

The objective of this study was to investigate the effect of Lipoderm Cream, VersaBase Gel, and Emollient Cream on the release and permeation of gabapentin formulated for neuropathic pain. Gabapentin of different strengths (1%, 5%, and 10%) was compounded with the bases, diffusion of the drug from thebases, and permeation through artificial skin model studied with Franz diffusionsystem. Steady-state flux, cumulative permeation, and lag times were calculated,and release mechanisms modelled with first order, second-order, Higuchi, Korsmeyer-Peppas, and Hixon-Crowell kinetic models. Gabapentin recovery from VersaBase Gel, Lipoderm Cream, and Emollient Cream was 100.8 ± 2.7%, 101.3 ± 1.2%, and 104.9 ± 3.3%, respectively. Gabapentin completely diffused out of the three bases within 6 hours of application according to the Higuchi model. Flux of the drug appeared to be concentration-dependent with no permeation occurring at 1% strength. Whereas, 5% and 10% strengths in Lipoderm Cream permeated the skin rapidly, the same concentrations in Emollient Cream and VersaBase Gel required 60-minutes and 120-minutes lag times, respectively. For the three bases, a strong correlation was observed between lag times and flux. The overall permeation in VersaBase Gel and Lipoderm Base was not significantly different (P>0.05). However, Emollient Cream resulted in a significantly lower total permeation compared to other bases (P<0.05). As the formulations are for pain management, products with no lag times and higher flux are preferable. Although VersaBase Gel and Emollient Cream displayed some gabapentin permeability, it is important to consider gabapentin stability in these bases prior to use.


Assuntos
Analgésicos , Gabapentina , Neuralgia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Composição de Medicamentos , Gabapentina/administração & dosagem , Gabapentina/farmacologia , Humanos , Manejo da Dor , Pele , Absorção Cutânea
13.
Pharm Res ; 36(12): 180, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728737

RESUMO

PURPOSE: To examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments. METHODS: Three acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a "reference" formulation (evaluated twice) was compared to the "test" in 10 subjects. Each application site was replicated to achieve greater statistical power with fewer volunteers. RESULTS: SC sampling revealed similarities and differences between products consistent with results from other surrogate bioequivalence measures, including dermal open-flow microperfusion experiments. Further analysis of the tape-stripping data permitted acyclovir flux into the viable skin to be deduced and drug concentration in that 'compartment' to be estimated. CONCLUSIONS: Acyclovir quantities determined in the SC, following a single-time point uptake and clearance protocol, can be judiciously used both to objectively compare product performance in vivo and to assess delivery of the active into skin tissue below the barrier, thereby permitting local concentrations at or near to the site of action to be determined.


Assuntos
Aciclovir/farmacocinética , Antivirais/farmacocinética , Creme para a Pele/farmacocinética , Aciclovir/administração & dosagem , Administração Tópica , Adulto , Antivirais/administração & dosagem , Disponibilidade Biológica , Transporte Biológico , Liberação Controlada de Fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Pele/metabolismo , Absorção Cutânea , Creme para a Pele/administração & dosagem , Equivalência Terapêutica
14.
AAPS PharmSciTech ; 21(1): 4, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728769

RESUMO

The purpose of present study was to develop a controlled release drug-in-adhesive patch for transdermal delivery of dexmedetomidine (Dex) using ion-pair technique. Based on the in vitro transdermal experiment, the role of ion-pair on the Dex release behavior and percutaneous absorption process was also investigated. Fourier transform infrared spectroscopy (FTIR), molecular modeling, differential scanning calorimetry (DSC), and rheological test were conducted to probe the effect of ion-pair on the Dex release from patch. Besides, the tape stripping test, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and molecular simulation were carried out to elaborate the action of ion-pair on the Dex percutaneous permeation process. Results showed that the optimized patch prepared with Dex-salicylic acid (SA) showed zero-order skin permeation profile within 24 h; Dex-SA had greater hydrogen bonding formation potential with pressure sensitive adhesive (PSA) than Dex, which resulted in the decrease in the formation ability of free volume of PSA and the increase with the improvement of mechanical strength and chain stiffness of PSA and thus controlled the release rate of Dex from transdermal patch. Besides, the physicochemical properties of Dex such as molecular weight and octanol/water partition coefficient were changed after forming ion-pair with SA, which decreased the permeation ability of Dex. In conclusion, a controlled release drug-adhesive patch for Dex was developed and the mechanism study of ion-pair on the Dex release and percutaneous permeation process was proposed at molecular level.


Assuntos
Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Adesivos , Animais , Preparações de Ação Retardada , Dexmedetomidina/química , Dexmedetomidina/farmacocinética , Ligações de Hidrogênio , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacocinética , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Peso Molecular , Ratos , Ratos Wistar , Reologia , Ácido Salicílico/química , Absorção Cutânea , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Adesivo Transdérmico
15.
Drug Deliv ; 26(1): 1104-1114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31735104

RESUMO

Nanoemulgels are composed of O/W nanoemulsion and hydrogels and are considered as ideal carriers for the transdermal drug delivery because these have high affinity to load hydrophobic drugs. The stable formulation of eprinomectin (EPR) is very challenging because of it is high hydrophobic nature. In this work, we have prepared EPR loaded nanoemulgel for the treatment of endo- and ectoparasites. The surface morphology of optimized formulations was characterized by scanning electron microscopy. Additionally, skin permeability and irritation tests were conducted for in vitro safety and in vivo skin retention and pearmeation test of EPR nanoemulgel were conducted for efficacy study. Obtained results indicated that the optimized formulation had good shear-thinning behavior, bioadhesiveness properties, and are nanosized droplets with porous internal structure, which are required for topical application. Furthermore, this formulation has showed good skin permeability in comparison to suspension and has no skin irritating property. Overall, the obtained results proved that nanoemulgel is a promising carrier for transdermal drug delivery and EPR nanoemulgel is a promising formulation for the treatment of endo- and ectoparasites.


Assuntos
Emulsões/química , Géis/química , Ivermectina/análogos & derivados , Pele/metabolismo , Administração Cutânea , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Géis/administração & dosagem , Ivermectina/administração & dosagem , Ivermectina/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas/química , Permeabilidade , Ratos , Ratos Sprague-Dawley , Absorção Cutânea
16.
Drug Des Devel Ther ; 13: 3307-3319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571832

RESUMO

Purpose: Hyaluronic acid-poly(ethylene glycol)-distearoyl phosphoethanolamine (HA-PEG-DSPE) modified and tocopheryl polyethylene glycol 1000 succinate (TPGS) contained nanostructured lipid carriers (NLCs) were prepared loading ropivacaine and dexmedetomidine to improve the topical anesthetic analgesic anesthesia efficiency. Methods: NLCs were prepared by the solvent diffusion method. The average particle size, zeta potential, release behavior, and cytotoxicity of the NLCs were tested. Ex vivo skin permeation was studied using a Franz diffusion cell mounted with depilated rat skin. Local anesthesia antinociceptive efficiency was evaluated by rat tail flick latency study in vivo. Results: NLCs have sizes of about 100 nm, with negative zeta potentials. All the NLCs formulations were found to be significantly less cytotoxic than free drugs at equivalent concentrations. The cumulative amount of drugs penetrated through rat skin from NLCs was 2.0-4.7 folds higher than that of the drugs solution. The in vivo anesthesia antinociception study displayed that NLCs showed stronger and longer anesthesia antinociceptive effect when compared with single drugs loaded NLCs and drugs solution even at a lower dosage of drugs. Conclusion: The results demonstrated that the HA modified, TPGS contained, dual drugs loaded NLCs could perform a synergistic effect and may reduce the amount of drugs, which can lower the toxicity of the system and at the meanwhile, increase the anesthesia antinociceptive efficiency.


Assuntos
Analgésicos/administração & dosagem , Anestésicos Locais/administração & dosagem , Dexmedetomidina/administração & dosagem , Portadores de Fármacos/química , Ropivacaina/administração & dosagem , Administração Cutânea , Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Animais , Células 3T3 BALB , Dexmedetomidina/farmacologia , Liberação Controlada de Fármacos , Ácido Hialurônico , Lipídeos , Camundongos , Nanopartículas , Nanoestruturas/administração & dosagem , Tamanho da Partícula , Fosfatidiletanolaminas/administração & dosagem , Fosfatidiletanolaminas/farmacologia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley , Ropivacaina/farmacologia , Absorção Cutânea , Vitamina E/administração & dosagem
17.
Int J Nanomedicine ; 14: 7561-7581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571864

RESUMO

Introduction: This study was conducted to elucidate the chemopreventive potential, cytotoxic, and suppression of cellular metastatic activity of etodolac (ETD)-loaded nanocarriers. Methods: To esteem the effect of charge and composition of the nanovectors on their performance, four types of vectors namely, negative lipid nanovesicles; phosalosomes (N-Phsoms), positive phosalosomes (P-Phsoms), nanostructured lipid carriers (NLCs) and polymeric alginate polymer (AlgNPs) were prepared and compared. ETD was used as a model cyclo-oxygenase-2 (COX-2) inhibitor to evaluate the potency of these nanovectors to increase ETD permeation and retention through human skin and cytotoxicity against squamous cell carcinoma cell line (SCC). Moreover, the chemopreventive activity of ETD nanovector on mice skin cancer model was evaluated. Results: Among the utilized nanovectors, ETD-loaded N-Phsoms depicted spherical vesicles with the smallest particle size (202.96±2.37 nm) and a high zeta potential of -24.8±4.16 mV. N-Phsoms exhibited 1.5, and 3.6 folds increase in the ETD amount deposited in stratum corneum, epidermis and dermis. Moreover, cytotoxicity studies revealed a significant cytotoxic potential of such nanovector with IC50=181.76 compared to free ETD (IC50=982.75), correlated to enhanced cellular internalization. Its efficacy extended to a reduction in the relative tumor weight with 1.70 and 1.51-fold compared to positive control and free ETD, that manifested by a 1.72-fold reduction in both COX-2 and proliferating cell nuclear antigen mRNA (PCNA-mRNA) levels and 2.63-fold elevation in caspase-3 level in skin tumors relative to the positive control group with no hepato-and nephrotoxicity. Conclusion: Encapsulation of ETD in nanovector enhances its in-vitro and in-vivo anti-tumor activity and opens the door for encapsulation of more relevant drugs.


Assuntos
Quimioprevenção , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Nanoestruturas/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/enzimologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/toxicidade , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Etodolac/farmacologia , Etodolac/uso terapêutico , Feminino , Humanos , Concentração Inibidora 50 , Lipídeos/química , Camundongos , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Estudos Prospectivos , Absorção Cutânea/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Eletricidade Estática , Resultado do Tratamento
18.
Int J Nanomedicine ; 14: 6555-6574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616143

RESUMO

Introduction: The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM. Methods: A 24 factorial experiment was constructed to inspect the impact of diverse variables on vesicles' features and sort out the optimal formula adopting Design Expert® software utilizing thin film hydration technique. Vesicles' evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations. Results: The optimal formula (PB15) showed spherical vesicles with EE% of 72.49±0.38%, PS of 559.30±10.70 nm, PDI of 0.57±0.15, ZP of -38.35±0.65 mV and Q6h of 59.60±0.24%. PB15 showed higher deformability index (28.39±5.71 g) compared to traditional bilosomes (5.88±0.90 g) and transethosomes (14.94±0.63 g). Further, PB15 showed superior skin permeation from rat's skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat's skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC0-48 and AUC0-∞ relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%. Conclusion: Overall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.


Assuntos
Ácidos e Sais Biliares/química , Sistemas de Liberação de Medicamentos , Olmesartana Medoxomila/administração & dosagem , Polietilenoglicóis/química , Administração Cutânea , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Masculino , Olmesartana Medoxomila/farmacocinética , Olmesartana Medoxomila/farmacologia , Tamanho da Partícula , Permeabilidade , Coelhos , Ratos Wistar , Pele/efeitos dos fármacos , Absorção Cutânea , Comprimidos
19.
J Cosmet Sci ; 70(5): 247-257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596229

RESUMO

Petrolatum is a mixture of hydrocarbons that is widely used as a moisturizer. It is incorporated in bodywash formulations to help hydrate and maintain healthy skin appearance. The aim of this study was to investigate skin deposition and penetration of petrolatum from an experimental bodywash system consisting of petrolatum in vitro. Experiments were performed using cadaver split-thickness skin and Franz diffusion cells. Radiolabeled 14C-dotriacontane (C32-alkane) was used as a model permeant for petrolatum. The bodywash was applied on the skin and subsequently rinsed. At predetermined time points, the skin was wiped to remove the residual material on the surface, and tape-stripping was performed. Petrolatum was observed to deposit from the bodywash when applied on split-thickness skin with simulated rinsing. Petrolatum then penetrated into the stratum corneum and was detected at the depth of 12 tape-stripping and in the epidermis. The bodywash formulation could provide significant deposition and penetration of petrolatum into the stratum corneum at 1-72 hours postapplication.


Assuntos
Epiderme , Vaselina , Células Epidérmicas , Absorção Cutânea
20.
SAR QSAR Environ Res ; 30(8): 561-585, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31535949

RESUMO

Current guidance for the estimation of dermal absorption (DA) of pesticides recommends the use of default values, read-across of information between formulations and in vitro testing. While QSARs exist to estimate percutaneous absorption, their use is currently not encouraged. Therefore, the potential of publicly available models for DA estimation was investigated based on data from 564 human in vitro DA experiments on pesticides. The classic Potts Guy model, the correction of Cleek Bunge for highly lipophilic chemicals, the mechanistic model of Mitragotri, and the COSMOS model were used to estimate the permeability coefficient kp. Different approaches were explored to calculate the percentage of external dose absorbed. IH SkinPerm was examined as stand-alone model. The models generally failed to accurately predict experimental values. For 30-40% of the predictions, there was overestimation by one order of magnitude. Three models underpredicted >10% of the cases, the remaining models <5%. DA of hydrophilic substances was typically underpredicted. Overprediction was more prominent for solid preparations and suspensions. The molecular weight, irritation potential and skin thickness did not correlate with the models' predictivity. Of the models investigated, IH SkinPerm performed best with 38% of the predictions within one order of magnitude and 2% underpredicted cases.


Assuntos
Praguicidas/metabolismo , Absorção Cutânea , Simulação por Computador , Humanos , Técnicas In Vitro , Modelos Biológicos , Relação Quantitativa Estrutura-Atividade
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