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The objective is to investigate the healing efficacy of a Chromolaena odorata layered-nitrile rubber transdermal patch on excision wound healing in rats. Wounds were induced in Sprague-Dawley rats and were later treated as follows: wound A, the negative control, received no treatment (NC); wound B, the negative control with an empty nitrile rubber patch (NC-ERP); wound C, treated with a C. odorata layered-nitrile rubber patch (CO-NRP); and wound D, the positive control with Solcoseryl gel with a nitrile rubber patch (PC-SG-NRP). After 1, 3, 6, 10, and 14 days, the rats were sacrificed and analyzed for wound contraction, protein content, hexosamine, and uronic acid levels. Macroscopic observation showed enhanced wound healing in wounds treated with CO-NRP with a wound contraction percentage significantly higher (p<0.05) on days 6 and 10 compared to those treated with NC-ERP. Similarly, protein, hexosamine, and uronic acid contents were also significantly higher (p<0.05) in CO-NRP-treated wounds when compared with wounds treated with NC-ERP. Histological findings showed denser collagen deposition and faster granulation tissue formation in wounds treated with CO-NRP. From the results obtained, it is concluded that the C. odorata layered-nitrile rubber transdermal patch was effective in healing skin wounds.
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Chromolaena , Goma , Ratas , Animales , Goma/metabolismo , Polímeros/metabolismo , Parche Transdérmico , Ratas Sprague-Dawley , Extractos Vegetales/farmacología , Cicatrización de Heridas , Piel/metabolismo , Colágeno/metabolismo , Ácidos Urónicos , HexosaminasRESUMEN
The wound-healing process is accelerated by inhibiting proteins that decelerate the wound-healing pathway. One of the active proteins involved in enhancing healing at the nuclear level and in gene expression is catenin. Inhibition of Glycogen Synthase Kinase 3ß (GSK3 ß) phosphorylates and degrades catenin via the downstream Wnt signalling pathway, thereby stabilizing catenin. A medicated wound dressing transdermal patch designed with fusion of bio wastes, viz. physiologically clotted fibrin, fish scale collagen, and the ethanolic extract of Mangifera indica (L.) and spider web, was analysed against GSK3ß to enhance healing. In our earlier studies, the compounds present in the transdermal patch were identified using GC-MS analysis; 12 compounds exhibiting the wound healing mechanism were analyzed using PASS software and filtered out. From these 12 compounds, 6 compounds that possessed drug-likeness were screened by SwissADME and vNN-ADMET to dock against GSK3ß in the present work. The PyRx results confirmed the binding of the six ligands to the active site of the target protein. Though the remaining filtered ligands also exhibited inhibitory activity, Molecular dynamics simulation studies were carried out with 100 ns on a complex of 10,12 Tricosadiyonic acid, Nopyl acetate and 2 Methyl 4 Heptanol as they showed binding affinity of -6.2Kcal/mol, -5.7Kcal/mol and -5.1Kcal/mol respectively. The stability of the complex was validated using MD simulation parameters RMSD, RMSF, Rg, and Number of Hydrogen bonds. These results implied that the transdermal patch would be efficient in accelerating the wound healing process through the inactivation of GSK3ß.Communicated by Ramaswamy H. Sarma.
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Glucógeno Sintasa Quinasa 3 , Extractos Vegetales , Animales , Extractos Vegetales/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Parche Transdérmico , beta Catenina/metabolismo , Cicatrización de Heridas , Vía de Señalización Wnt/fisiología , Simulación del Acoplamiento MolecularRESUMEN
This study aimed to prepare colchicine (CO), 4-hydroxyacetophenone (HA), and protocatechuic acid (CA) contained in transdermal rubber plasters into a more releasable and acrylate pressure-sensitive adhesive (PSA) to optimize traditional Touguling rubber plasters (TOU) with enhanced transdermal permeability by using deep eutectic solvents (DES) technology. We compared the difference in the release behavior of CO between rubber plaster and PSA, determined the composition of the patch through pharmacodynamic experiments, explored the transdermal behavior of the three components, optimized the patch formula factors, and improved the penetration of CO through the skin. We also focused on elucidating the interactions among the three components of DES and the intricate relationship between DES and the skin. The melting point of DES was determined using DSC, while FTIR, 13C NMR, and ATR-FTIR were used to explore the intricate molecular mechanisms underlying the formation of DES, as well as its enhancement of skin permeability. The results of this investigation confirmed the successful formation of DES, marked by a discernible melting point at 27.33°C. The optimized patch, formulated with a molar ratio of 1:1:1 for CO, HA, and CA, significantly enhanced skin permeability, with the measured skin permeation quantities being 32.26 ± 2.98 µg/cm2, 117.67 ± 7.73 µg/cm2, and 56.79 ± 1.30 µg/cm2 respectively. Remarkably, the optimized patch also demonstrated similar analgesic and anti-inflammatory effects compared to commercial diclofenac diethylamide patches in different pharmacodynamics studies. The formation of DES altered drug compatibility with skin lipids and increased retention, driven by the interaction among the three component molecules through hydrogen bonding, effectively shielding the skin-binding sites and enhancing component permeation. In summary, the study demonstrated that optimized DES patches can concurrently enhance the penetration of CO, HA, and CA, thereby providing a promising approach for the development of DES in transdermal drug delivery systems. The findings also shed light on the molecular mechanisms underlying the transdermal behavior of DES and offer insights for developing more effective traditional Chinese medicine transdermal drug delivery systems.
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Disolventes Eutécticos Profundos , Absorción Cutánea , Colchicina/metabolismo , Colchicina/farmacología , Goma/metabolismo , Goma/farmacología , Administración Cutánea , Piel/metabolismo , Parche TransdérmicoRESUMEN
Current study reports the combined technique of microneedle array patches and thermoresponsive gels. Microneedles array patch mediated insitu skin depots were evaluated for sustain drug delivery using sodium alginate/Poly (vinylcaprolactam) thermoresponsive gels. Their phase transition property from sol-gel state was monitored with AR2000 rheometer. Ibuprofen sodium was loaded in optimized formulations. The non-soluble cross-linked microneedle array patches (MAPs) were prepared from variable biocompatible polymers using silicone micromoulds. The fabricated MAPs were evaluated for mechanical stability, inskin dissolution, insertion forces and moisture contents. The penetration depth of MAPs in neonatal rabbit skin was tracked by optical coherence tomography. The optimized MAPs (GP10000) were used as microporation source in skin owing to their stable nature. Pores formation in skin samples after MAPs treatment was confirmed by optical coherence tomography, dye binding and skin integrity analysis. The invitro permeation of Ibuprofen sodium from formulations was studied using Franz cells across intact skin and MAPs applied skin. It was concluded from the results that Ibuprofen sodium permeation was observed for longer time through MAPs treated skin as compared to intact skin. Confocal study confirmed the diffusion of drug loaded formulations in deeper tissues with higher intensity.
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Alginatos , Ibuprofeno , Animales , Conejos , Ibuprofeno/farmacología , Alginatos/química , Administración Cutánea , Sistemas de Liberación de Medicamentos/métodos , Geles , Sodio , Parche TransdérmicoRESUMEN
The objective of the present study was to fabricate microneedles for delivering lipophilic active ingredients (APIs) using digital light processing (DLP) printing technology and quality by design (QbD) supplemented by artificial intelligence (AI) algorithms. In the present study, dissolvable microneedle (MN) patches using ibuprofen (IBU) as a model drug were successfully fabricated with DLP printing technology at â¼ 750 µm height, â¼250 µm base diameter, and tip with radius of curvature (RoC) of â¼ 15 µm. MN patches were comprised of IBU, photoinitiator, Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP), polyethylene glycol dimethacrylate (PEGDAMA)550 and distilled water and were developed using the QbD optimization approach. Optimization of print fidelity and needle morphology were achieved using AI implementing a semi-supervised machine learning approach. Mechanical strength tests demonstrated that IBU MNs formed pores both on Parafilm M® and human cadaver skin. IBU-MNs consisting of 0.23 %w/v and 0.49 %w/v LAP with 10 %w/v water showed â¼ 2 mg/cm2 sustained drug permeation at 72 h in skin permeation experiments with flux of â¼ 40 µg/cm2/h. Pharmacokinetic studies in rats displayed biphasic rapid first-order absorption with sustained zero-order input of Ko = 150ug/hr, AUC0-48h = 62812.02 ± 11128.39 ng/ml*h, Tmax = 2.66 ± 1.12 h, and Cmax = 3717.43 ± 782.25 ng/ml (using 0.23 %w/v LAP IBU MN patch). An in vitro in vivo relation (IVIVR) was conducted identifying a polynomial relationship between patch release and fraction absorbed in vivo. This study demonstrates fabrication of dissolvable DLP-printed microneedle patches for lipophilic API delivery with biphasic rapid first-order and sustained zero-order release.
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Inteligencia Artificial , Piel , Humanos , Ratas , Animales , Administración Cutánea , Preparaciones Farmacéuticas , Sistemas de Liberación de Medicamentos , Ibuprofeno , Impresión Tridimensional , Agujas , Parche TransdérmicoRESUMEN
Innovations on materials and technologies have greatly promoted the rapid development of wearable electronics from disease diagnosis to therapeutics. For superficial skin tumors, skin-attachable patches possess the advantages of minimally invasive property, alleviative side effects, and high efficiency. The development of noninvasive techniques and devices is still in urgent demands. Here, a flexible skin patch fabricated through a facile preparation method is reported for noninvasive hybrid thermophysical therapy and adaptative immune function enhancement. The liquid metal enabled skin patch is demonstrated with high conductivity, certain stability, biocompatibility, and an enhanced adhesive merit on skin surfaces for cryoablation therapy and magnetic hyperthermia therapy. The skin patch exhibits remarkably conformable heating and cooling performance toward the treatment of 4T1 breast tumors. The magnetic resonance images also indicate the significant tumor ablation effect. Interestingly, a relatively stable proportion of both CD8+ T and CD4+ T cells in the peripheral blood is identified after tumor therapy in comparison with the decreased trend in the untreated group, representing an efficient antitumor immune response induced by the skin patch. The developed skin patch would provide a promising noninvasive approach for tumor therapies by direct tumor destruction and maintenance of the antitumor immune response.
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Hipertermia Inducida , Neoplasias Cutáneas , Dispositivos Electrónicos Vestibles , Humanos , Parche Transdérmico , InmunidadRESUMEN
BACKGROUND: Chronic pain represents a significant and costly healthcare problem especially in the older patient. Transdermal opioid therapy is easy to apply and ensures constant supply of active ingredients. However, skin irritation, poor adhesion and systemic side effects complicate transdermal pain therapy. METHODS: In the Relief study, comprising 54 centers, all in Germany, 252 patients were recruited and data about the general care situation as well as the characteristics, effects and side effects of the Aloe vera fentanyl patch were collected. 92 patients had a prior treatment with fentanyl patch without Aloe vera, allowing a comparative analysis. RESULTS: Compared to patches without Aloe vera, the new fentanyl patch showed better adhesion. Systemic and local tolerance and pain reduction were also significantly better. Patients also reported improvements in side effects and central parameters of quality of life. The data regarding the care situation in Germany showed remarkably low use of coanalgetics and laxatives in pain patients. DISCUSSION: Aloe vera in transdermal pain treatment improves adhesion and local tolerance of the patch. Pain control and quality of life were also improved. Regional care data concerning cotreatment in pain therapy from this study indicate a lack of penetration of existing guidelines in general practitioners' pain therapy.
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Aloe , Fentanilo , Humanos , Fentanilo/efectos adversos , Calidad de Vida , Analgésicos Opioides/efectos adversos , Dolor/tratamiento farmacológico , Administración Cutánea , Parche TransdérmicoRESUMEN
Chemical leucoderma is defined as hypopigmentation or vitiligo-like hypomelanosis caused by repeated chemical exposure, and the diagnosis can be made clinically. Chemical leucoderma induced by fentanyl transdermal patches is rare. This case report involves a 53-year-old man with chronic back pain caused by herniated nucleus pulposus at the L4-L5 level. The patient had used fentanyl transdermal patches for about 2 years. Depigmented lesions were observed in the areas where fentanyl transdermal patches had been applied. Chemical leucoderma was the most likely diagnosis. There remains a debate regarding whether there is a fentanyl dose-response relationship and whether the duration of exposure is relevant. Spontaneous repigmentation may occur after discontinuing the chemical exposure, and follow-ups are recommended to monitor whether spontaneous repigmentation occurs. Additionally, several treatment options have been proposed as specific treatments for chemical leucoderma, including psoralens, corticosteroids, calcineurin inhibitors, immunosuppressive agents and phototherapy.
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Albinismo Oculocutáneo , Hipopigmentación , Vitíligo , Masculino , Humanos , Persona de Mediana Edad , Fentanilo/efectos adversos , Hipopigmentación/inducido químicamente , Hipopigmentación/patología , Vitíligo/patología , Parche Transdérmico , Analgésicos Opioides/efectos adversos , Administración CutáneaRESUMEN
BACKGROUND: Chronic neuropathic pain is a disabling condition that affects quality of life. Despite recommendations and guidelines, treatment remains suboptimal as it often does not result in significant symptom relief. Capsaicin 8% patch has been used for the treatment of several peripheral neuropathic pain etiologies with encouraging results. OBJECTIVES: To assess the results of capsaicin 8% patch on neuropathic pain by evaluating pain intensity and the painful treatment area. STUDY DESIGN: Observational retrospective cohort study. SETTING: All patients submitted to capsaicin treatment at the Chronic Pain Unit of the Hospital Centre of Tondela Viseu, from 2011 through 2019. METHODS: Records of capsaicin treatments were reviewed, and the data collected. The primary outcome was pain intensity and painful treatment area reduction between the first and last treatment. Also, the number of treatments performed, neuropathic pain duration, anatomic location, pain etiology, and concomitant oral pain medication at baseline and upon treatment conclusion was also listed. RESULTS: Postsurgical neuropathic pain was the most common etiology (49%), followed by postherpetic (28%). The median (interquartile range [IQR]) baseline pain intensity assessed by the Numeric Rating Scale (NRS-11) was 6 (5-8) and the median (IQR) final NRS-11 was 3 (1-5), with a median (IQR) relative difference of -0.5 (-0.85-0.17) with statistically significant differences (P < 0.001) between baseline and last pain intensity, regarding all groups. Also, there was a reduction in the painful treatment area between baseline and the last evaluation, with a median (IQR) relative difference of -0.4 (-0.625-0.167). LIMITATIONS: A relatively small sample and occasional different timing for pain intensity and pain treatment area assessment due to logistical difficulties. CONCLUSIONS: Capsaicin 8% patch is a valuable option for the treatment of peripheral neuropathic pain, providing a significant reduction in pain intensity and painful area. It is well tolerated and has a high treatment compliance.Ethics Committee Reference Number: 16/16//04/2021.
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Capsaicina , Neuralgia , Capsaicina/uso terapéutico , Humanos , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Calidad de Vida , Estudios Retrospectivos , Parche TransdérmicoRESUMEN
Adequate micronutrient availability is particularly important in women, children and infants. Micronutrient deficiencies are the major cause of maternal and neonatal morbidity. To overcome this, WHO recommends the use of folic acid and iron supplements for reducing anaemia and improving the health of the mother and infants. Oral intake of supplements for nutritional deficiencies are associated with gastric irritation, nausea, constipation and non-patient compliance due to associated taste. In case of absorption deficiency nutrients administered orally pass-through digestive tract unabsorbed. In the present study, we propose transdermal delivery of nutraceuticals to avoid the limitations associated with oral intake. Transdermal delivery has limited use because of the closely packed barrier of the stratum corneum that limits the permeability of molecules across skin. Here, we have used biomimetic nanovesicles impregnated in transdermal patches for delivery of folic acid and iron. Nanovesicles are prepared using an abundant component of cell membrane, phosphatidyl choline and a permeation enhancer. Further these nanovesicles are impregnated onto polyacrylate based transdermal patch.In vitrostudies have shown the ability of nanovesicles to fluidise skin lipids and penetrate into deeper skin.In vivoapplication of transdermal patches gradually increased the systemic concentration of nutraceuticals. Post application of the patch, five-fold increase in plasma folic acid concentration and 1.5-fold increase in plasma iron concertation was achieved in 6 h. Developed nanovesicles were compatible with keratinocytes and fibroblasts as testedin vitroand have the potential to enhance the cellular uptake of molecules. Skin irritation studies on human volunteers have confirmed the safety of nutraceutical loaded nanovesicles. Thus, the developed nutraceutical loaded transdermal patches provide a potential, easy to use platform for micronutrient delivery in infants and mothers.
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Deficiencias de Hierro , Parche Transdérmico , Niño , Suplementos Dietéticos , Sistemas de Liberación de Medicamentos , Femenino , Ácido Fólico/metabolismo , Humanos , Recién Nacido , Hierro , Mentol/metabolismo , Micronutrientes/metabolismo , Fosfolípidos/metabolismo , Piel/metabolismo , Absorción CutáneaRESUMEN
INTRODUCTION: Treating hair loss of Alopecia areata is a quite challenge. The treatment not only needs to be effective but must meet specific requirements in terms of accurate dose, sustain release, comfortable application with aesthetic appearance. Thus, the study was designed to develop sustained release topical patches releasing allicin using different sources, including the extract from fresh and aged garlic, and commercially pure one. METHODS: Patches were formulated by solvent casting method using ethylene-vinyl acetate as backing layer and Carbopol® 971P NF (CP) as mucoadhesive polymer. Physicochemical properties were evaluated including weight, thickness, drug content, surface pH, moisture content, folding endurance, and swelling. In addition to in vitro diffusion study across the cellulose and Strat-M® membranes. RESULTS: Patches showed good physicochemical properties. No significant difference (p > 0.05) was obvious in the percentage of allicin diffused across cellulose membrane between patch A (loaded with commercial allicin), patch B1 (loaded with fresh garlic extract), and patch C (loaded with aged garlic extract). However, ethanol enhanced the diffusion of allicin. The percentage of allicin diffused across cellulose membrane over 20 h from patch E (45 mg CP, 2 mL fresh garlic extract-equivalent to 60 mg allicin-and 1 mL of ethanol) was 79.94%. The flux and permeability coefficients were 2.62 mg/cm2 /h and 0.52 cm/h, respectively, with an enhancement ratio of 2.60 times the reference patch M (mashed garlic). CONCLUSION: Promising development of topical patches of allicin using garlic extract as natural source with lower cost than the commercial pure allicin and higher aesthetic acceptance than the used mashed garlic.
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Disulfuros/administración & dosificación , Ajo , Ácidos Sulfínicos/administración & dosificación , Parche Transdérmico , Humanos , Extractos VegetalesRESUMEN
INTRODUCTION: The use of topical agents has been suggested for post-surgical neuropathic pain. A high-concentration capsaicin 179-mg cutaneous patch (Qutenza™) is licensed in adults for chronic neuropathic pain in the EU, and neuropathic pain with post-herpetic neuralgia and neuropathic pain with diabetic peripheral neuropathy in the USA. This article aims to describe the use of a topical capsaicin 179-mg cutaneous patch in the treatment of PSNP. AREA COVERED: This narrative review presents the relevant clinical aspects of the use of a topical capsaicin 179-mg cutaneous patch for the treatment of post-surgical neuropathic pain (PSNP). Randomized control trials, observational studies, case series, and reports investigating the clinical use of the capsaicin patch were searched through MEDLINE, EMBASE, AMED, Cochrane Library, CINAHL, Web of Science, and ROAD databases. Trials from citation lists of reviewed articles and hand-searching were added. The search concluded in September 2020. 10/20 articles were considered. EXPERT OPINION: Some clinical studies demonstrated the efficacy of the capsaicin 179-mg patch in PSNP as monotherapy and concomitant treatment with oral treatments. This topical treatment of PSNP is better tolerated and accepted compared with systemic treatments. To maximize the effectiveness of the treatment, correct administration recommendations should be followed.
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Neuropatías Diabéticas , Neuralgia Posherpética , Neuralgia , Adulto , Capsaicina/uso terapéutico , Humanos , Neuralgia/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Parche TransdérmicoRESUMEN
It has proven challenging to quantify 'drug input' from a formulation to the viable skin because the epidermal and dermal targets of topically applied drugs are difficult, if not impossible, to access in vivo. Defining the drug input function to the viable skin with a straightforward and practical experimental approach would enable a key component of dermal pharmacokinetics to be characterised. It has been hypothesised that measuring drug uptake into and clearance from the stratum corneum (SC) by tape-stripping allows estimation of a topical drug's input function into the viable tissue. This study aimed to test this idea by determining the input of nicotine and lidocaine into the viable skin, following the application of commercialised transdermal patches to healthy human volunteers. The known input rates of these delivery systems were used to validate and assess the results from the tape-stripping protocol. The drug input rates from in vivo tape-stripping agreed well with the claimed delivery rates of the patches. The experimental approach was then used to determine the input of lidocaine from a marketed cream, a typical topical product for which the amount of drug absorbed has not been well-characterised. A significantly higher delivery of lidocaine from the cream than from the patch was found. The different input rates between drugs and formulations in vivo were confirmed qualitatively and quantitatively in vitro in conventional diffusion cells using dermatomed abdominal pig skin.
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Epidermis/metabolismo , Absorción Cutánea , Crema para la Piel/farmacocinética , Parche Transdérmico , Administración Cutánea , Adulto , Animales , Evaluación Preclínica de Medicamentos/métodos , Femenino , Voluntarios Sanos , Humanos , Lidocaína/administración & dosificación , Lidocaína/farmacocinética , Masculino , Nicotina/administración & dosificación , Nicotina/farmacocinética , Crema para la Piel/administración & dosificación , PorcinosRESUMEN
Sustained release of drugs over a pre-determined period is required to maintain an effective therapeutic dose for variety of drug delivery applications. Transdermal devices such as polymeric microneedle patches and other microneedle-based devices have been utilized for sustained release of their payload. Swift clearing of drugs can be prevented either by designing a slow-degrading polymeric matrix or by providing physiochemical triggers to different microneedle-based devices for on-demand release. These long-acting transdermal devices prevent the burst release of drugs. This review highlights the recent advances of microneedle-based devices for sustained release of vaccines, hormones, and antiretrovirals with their prospective safe clinical translation.
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Preparaciones de Acción Retardada/administración & dosificación , Portadores de Fármacos/química , Piel/metabolismo , Parche Transdérmico , Administración Cutánea , Animales , Ensayos Clínicos como Asunto , Preparaciones de Acción Retardada/farmacocinética , Composición de Medicamentos/métodos , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Humanos , Modelos Animales , Agujas , Polímeros/química , SolubilidadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Siegesbeckiae Herba (SiH) is a traditional anti-rheumatic herbal medicine in China. A SiH derived product, Phynova Joint and Muscle Relief Tablets™, has been granted the UK license in 2015. Although transdermal delivery provides better patient compliance and relative constant plasma drug concentration, the feasibility of transdermal delivery of SiH was not clear. AIM OF THE STUDY: The aim of the present study was to develop a novel transdermal patch containing SiH extract for alternative therapy of rheumatoid arthritis. MATERIALS AND METHODS: SiH extract containing 48.5% (w/w) of kirenol was prepared from Siegesbeckia pubescens Makino. Then transdermal patches containing SiH extract were prepared by the solvent evaporation technique. The formulation of the transdermal patch was optimized based on the in vitro skin permeation experiment. Finally, the anti-inflammatory and analgesic activity of the optimal patch were evaluated by chronic inflammation model induced by complete Freund's adjuvant (CFA) and writhing model induced by acetic acid, separately. RESULTS: Oleic acid (OA) showed the maximum permeation enhancement effect with the enhancement ratio (ER) values of 3.32. Therefore, OA was used as a permeation enhancer in the transdermal patch. The optimal formulation consisted of SiH extract (10% of the matrix, w/w), OA (10% of the matrix, w/w), DURO-TAK® 87-2287 (pressure sensitive adhesive matrix) and Scotchpak™ 9701 (backing layer). The optimal transdermal patch containing SiH extract significantly reduced the degree of paw swelling and number of writhing in inflammation model and writhing model, respectively. CONCLUSIONS: The developed transdermal patch containing Siegesbeckiae Herba extract showed good anti-inflammatory and analgesic effects, which demonstrated a great potential for alternative therapy of rheumatoid arthritis.
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Antirreumáticos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Extractos Vegetales/farmacología , Analgésicos/administración & dosificación , Analgésicos/aislamiento & purificación , Analgésicos/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antirreumáticos/administración & dosificación , Antirreumáticos/aislamiento & purificación , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Artritis Reumatoide/patología , Asteraceae/química , Diterpenos/administración & dosificación , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Adyuvante de Freund , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Ratas , Ratas Wistar , Parche TransdérmicoRESUMEN
OBJECTIVE: Placebo effects may occur when it is known that an inert substance is given (i.e., open-label placebo). It is not yet clear whether these effects are similar to concealed (i.e., closed-label) placebo effects for itch or whether nocebo effects can be induced under open-label conditions. METHODS: Healthy volunteers (n = 112) were randomized to an open-label (I) or closed-label (II) positive suggestions group, or an open-label (III) or closed-label (IV) negative suggestions group. Participants were told, as cover story, that a transdermal caffeine patch would be applied that positively influences cognitive abilities and, as a side effect, positively or negatively (depending on group allocation) influences itch. Participants in the open-label groups were given a rationale explaining placebo and nocebo effect mechanisms. Itch (the primary outcome) was induced at baseline and postsuggestions by histamine iontophoresis. RESULTS: Analyses of variance revealed significantly lower itch in the positive compared with the negative suggestions groups for both open- and closed-label contexts (all, p ≤ .008, Cohen d ≥ 0.47). Self-rated skin response was less severe after positive versus negative suggestions (all, p ≤ .017, Cohen d ≥ 0.33), but no effects on physical skin response were found (all, p ≥ .23, Cohen d ≤ 0.30). CONCLUSIONS: Itch can be reduced by positive compared with negative suggestions under both open- and closed-label conditions. These findings indicate that open-label suggestions may potentially be a tool to use placebo effects for self-reported outcomes in clinical practice, for example, by explaining the role of expectancy in treatment. It needs to be investigated further under which circumstances an open-label rationale may impact placebo and nocebo effects.Trial Registration:www.trialregister.nl; NTR7174.
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Efecto Nocebo , Parche Transdérmico , Humanos , Efecto Placebo , Prurito , SugestiónRESUMEN
Wheat allergy is a pathological event involving immunocompetent cells against ingested wheat allergen and is clearly associated with transdermal sensitization. However, the molecular mechanisms involved in the disease etiology are not completely understood. A complex cellular and tissue network linking to food allergy makes it difficult to understand the molecular mechanism of allergenicity. Animal models are valuable tools to deduce basic principles of human disease without invasive intervention trials. A mouse model of wheat allergy has provided insights into effects of skin exposure to wheat protein; it is a plausible route of human sensitization for wheat anaphylaxis. Further investigation of this model will capture the essential occurrence and flow of events, bringing useful clues to develop effective treatment and control strategies against wheat allergy. Here, we describe a method for analyzing the expression of cell surface molecules in single cells isolated from lymphoid tissue with flow cytometry. Sensitization by wheat extracts significantly increases antigen-specific T cells in the spleen. Collecting information regarding the contribution of immune cells to allergic sensitization in the development of wheat allergy would be useful in preventing and treating food allergies.
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Modelos Animales de Enfermedad , Inmunofenotipificación/métodos , Linfocitos/efectos de los fármacos , Extractos Vegetales/inmunología , Triticum/inmunología , Hipersensibilidad al Trigo/inmunología , Administración Cutánea , Animales , Antígenos CD/genética , Antígenos CD/inmunología , Biomarcadores/metabolismo , Femenino , Harina/análisis , Citometría de Flujo , Expresión Génica , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Ganglios Linfáticos/citología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Linfocitos/citología , Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/administración & dosificación , Análisis de la Célula Individual , Bazo/citología , Bazo/efectos de los fármacos , Bazo/inmunología , Parche Transdérmico , Triticum/química , Hipersensibilidad al Trigo/sangre , Hipersensibilidad al Trigo/genética , Hipersensibilidad al Trigo/patologíaRESUMEN
The development of microneedles (MNs) assisted drug delivery technologies have been highly active for more than two decades. The minimally invasive and self-administered MN technology bypasses many challenges associated with injectable drug delivery systems, by delivering the therapeutic materials directly into the dermal and ocular space and allowing the release of the active ingredient in a sustained or controlled manner. Different types of MNs (biodegradable solid/dissolving MNs and nanoparticle loaded/coated polymeric MNs or delivery by hollow MNs) have been envisioned for long-acting sustained delivery of therapeutic payloads, with the aim of reducing the side effects and administration frequency to improve the patient compliance. In this review, we covered the different types of MNs loaded with different nano/biotherapeutics for long-acting delivery for a wide range of potential clinical applications. We also outlined the future development scenario of such long-acting MN delivery systems for different disease conditions to achieve improved clinical benefit. Finally, we discussed the challenges lie ahead to realize the full potential of sustained-release long-acting MNs in the clinic.
Asunto(s)
Preparaciones de Acción Retardada/administración & dosificación , Portadores de Fármacos/química , Parche Transdérmico , Administración Cutánea , Animales , Preparaciones de Acción Retardada/farmacocinética , Composición de Medicamentos/métodos , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Humanos , Cumplimiento de la Medicación , Modelos Animales , Nanopartículas/química , Agujas , Polímeros/química , Piel/metabolismoRESUMEN
Current therapy of tuberculosis (TB) has several limitations, such as risk of liver injury and intestinal dysbiosis due to frequent oral administration of antibiotics. Transdermal administration could be used to improve antibiotic delivery for treatment of Mycobacterium tuberculosis infection. Therefore, we developed a novel approach, using hydrogel-forming microneedle (MN) arrays to transdermally deliver TB drugs, namely rifampicin, isoniazid, pyrazinamide and ethambutol, which have different physicochemical properties. These drugs were individually prepared into three types of drug reservoirs, including lyophilised tablets, directly compressed tablets and poly(ethylene glycol) tablets. Formulations of each drug reservoir type were optimised to achieve a rapidly dissolving tablet, and further integrated with hydrogel-forming MN arrays for in vitro permeation studies. Three types of hydrogel formulation were manufactured using different type of polymers and crosslinking processes. These MN arrays were then evaluated in terms of swelling ability, morphology and physical properties. Results of solute diffusion studies showed that drug permeation across the swollen hydrogel membrane was affected mostly by physiochemical properties and functional groups of each drug. In the in vitro studies, the amount of permeated drug through the hydrogel-forming MN arrays across the dermatomed neonatal porcine skin was affected by the drug solubility and reservoir design. The highest permeation of rifampicin (3.64 mg) and ethambutol (46.99 mg) were achieved using MN arrays combined with the poly(ethylene glycol) tablets and directly compressed tablet, respectively. For isoniazid and pyrazinamide, the highest drug permeation was attained using lyophilised reservoir with the amount of drug delivered approximately 58.45 mg and 20.08 mg, respectively. These equate to transdermal delivery of approximately 75% (rifampicin), 79% (isoniazid), 20% (pyrazinamide) and 47% (ethambutol) of the drugs loaded into the reservoirs on average. Importantly, the results of this work have demonstrated the versatility of hydrogel formulations to deliver a TB drug regime using MN arrays. Accordingly, this is a promising approach to deliver high dose of TB drugs.
Asunto(s)
Antituberculosos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Tuberculosis/tratamiento farmacológico , Administración Cutánea , Animales , Animales Recién Nacidos , Antituberculosos/química , Antituberculosos/farmacocinética , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/instrumentación , Evaluación Preclínica de Medicamentos , Liofilización , Humanos , Hidrogeles , Agujas , Permeabilidad , Absorción Cutánea , Solubilidad , Porcinos , Distribución Tisular , Parche TransdérmicoRESUMEN
A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.