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OBJECTIVE@#To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design.@*METHODS@#Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators.@*RESULTS@#Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed.@*CONCLUSION@#Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Administration, Cutaneous , Drugs, Chinese Herbal , Intestinal Neoplasms , Intestinal Obstruction , Drug Therapy , Ultrasonic Therapy , MethodsABSTRACT
Topically applied traditional Chinese medicines (TCM) generally show low transdermal rates and doses, leading to weak therapeutic efficacy. Here, cataplasm of white mustard seed varnish was prepared. The effects of iontophoresis and sonophoresis on the transdermal delivery of this TCM and its anti-asthma effect were evaluated. Active components of white mustard seed, rhizoma corydalis and Radix Kansui were obtained after alcohol extraction, respectively. The volatile oil in Asarum Heterotropoides were obtained with volatile oil extraction equipment. The drug loading ratio of cataplasms was 17% (w/w). Franz cell diffusion method was used to evaluate the accumulated permeation amount and the steady-state transdermal absorption rate of sodium thiocyanate. The improvement of sonophoresis on transdermal absorption was higher than that of iontophoresis.Asthma model of guinea pigs were established. Cataplasms of white mustard seed varnish were applied on the back of guinea pigs. Iontophoresis and sonophoresis obviously promoted the transdermal absorption and enhanced anti-asthma efficacy of white mustard seed varnish cataplasms. Pathological analysis showed that iontophoresis and sonophoresis significantly alleviated inflammation. Compared with the model group, IL-4 and IgE levels in the cataplasm group, cataplasm/iontophoresis group, cataplasm/sonophoresis group decreased obviously, although the IFN-γ levels markedly increased. Moreover, the therapeutic efficacy of cataplasm/sonophoresis group was the best in all the groups, even leading to levels similar to that of healthy animals. Iontophoresis and sonophoresis are effective methods to promote transdermal absorption of cataplasms. Moreover, the effect of sonophoresis is higher than that of iontophoresis. Physical penetration improvement techniques provide a novel insight for the wide application of transdermal TCM.
ABSTRACT
Topical drug delivery is an interesting approach to treat skin diseases and to avoid pain and low patient compliance in cases where a systemic delivery is required. However, the stratum corneum, which is the outermost skin layer, strongly protects the body from the entrance of substances, especially those hydrophilic. In this context, different physical methods have been studied to overcome the stratum corneum barrier and facilitate penetration of drugs into or through the skin. Among them, iontophoresis, low-frequency ultrasound and microneedles have been widely employed for transdermal drug delivery. More recently, they are also studied to aid in the treatment of dermatological disorders, such as skin tumors and inflammation. Basically, iontophoresis refers to the movement of charged and non-charged hydrophilic molecules through the skin due to the application of a low constant electric current and the contributions of electromigration and electroosmosis. In low-frequency ultrasound, cavitation is the main mechanism for skin permeabilization that consists on the formation of microbubbles that disorganize the stratum corneum. Microneedles are microprojections, minimally invasive, that can be designed with different lengths, materials and geometry to increase skin permeability. In this review, concepts, mechanisms and applications of these three physical methods will be presented and discussed with focus on their use in dermatological treatments. Moreover, comparative studies using different physical methods will be presented and also some clinical perspectives will be addressed
Subject(s)
Skin , Administration, Topical , Skin Diseases/drug therapy , Ultrasonics/methods , Administration, Cutaneous , Iontophoresis/methodsABSTRACT
Objective To compare the improvement effect of three physical techniques on the transdermal absorption of sinap?ine thiocyanate(ST)in vitro,including microneedles,sonophoresis and iontophoresis,and to evaluate the mechanism and rules of physcial techniques on the transdermal absorption of poorly transdermal absorbed drugs. Methods In vitro transdermal experiment was carried out under the circumstances of microneedles,sonophoresis or iontophoresis,using the modified Franz diffusion pool. The 2 mg/ml ST solution was adopted as the donor solution, and the SD rats′abdomen skin was used as the model skin. Sampling was car?ried out at the predetermined time points and each sample was analyzed by HPLC. Cumulative transdermal amount and steady transder?mal absorption rate were calculated. Pathological slides were made after the skins were treated with microneedles ,sonophoresis and iontophoresis for 12 h. The structure changes were observed to evaluate the transdermal improvement mechanism of different technolo?gies. Results Accumulated transdermal amount of ST was little without any techniques. The transdermal improvement effect of differ?ent technologies was as follows:microneedles>sonophoresis>iontophoresis. A substantial hole formed on the skin by microneedles to promote ST transdermal absorption obviously. Sonophoresis disrupted the tight structure of skin and improved the transdermal absorp?tion of drugs easily. The effect of iontophresis on skin structure was little. Conclusion This study provides experimental evidence for choice of different techniques to improve transdermal absorption.
ABSTRACT
Objective To compare the improvement effect of three physical techniques on the transdermal absorption of sinapine thiocyanate(ST)in vitro, including microneedles, sonophoresis and iontophoresis, and to evaluate the mechanism and rules of physcial techniques on the transdermal absorption of poorly transdermal absorbed drugs. Methods In vitro transdermal experiment was carried out under the circumstances of microneedles, sonophoresis or iontophoresis, using the modified Franz diffusion pool. The 2 mg/ml ST solution was adopted as the donor solution, and the SD rats′ abdomen skin was used as the model skin. Sampling was carried out at the predetermined time points and each sample was analyzed by HPLC. Cumulative transdermal amount and steady transdermal absorption rate were calculated. Pathological slides were made after the skins were treated with microneedles, sonophoresis and iontophoresis for 12 h. The structure changes were observed to evaluate the transdermal improvement mechanism of different technologies. Results Accumulated transdermal amount of ST was little without any techniques. The transdermal improvement effect of different technologies was as follows: Microneedles>sonophoresis>iontophoresis. A substantial hole formed on the skin by microneedles to promote ST transdermal absorption obviously. Sonophoresis disrupted the tight structure of skin and improved the transdermal absorption of drugs easily. The effect of iontophresis on skin structure was little. Conclusion This study provides experimental evidence for choice of different techniques to improve transdermal absorption.
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The present study was designed to evaluate the effect of low-frequency ultrasound on transdermal delivery of insulin as an ointment. This was conducted in the proceeding of a previously published paper by the authors. Forty-two Wistar rats were randomly divided into 7 groups including one control and six experimental groups with six rats in each group. An ointment of insulin was prepared and applied (alone and with low-frequency ultrasound) on the skin of animals. In all the groups, blood samples were collected from the tail vein of the animals every 15 minutes of the whole 90-minute experimental period. The changes of blood glucose levels with time were assessed in the groups. The results of this study showed that the exposure of the insulin ointment to low-frequency ultrasound for a period of 60 minutes significantly decreased its potency in lowering the blood glucose levels. We conclude that eucerin impedes transdermal insulin delivery by sonophoresis in rats. We suggest that the lowering effect of ultrasound on the penetration ability of insulin is probably due to its effect on the specific molecular structure formed between the insulin and the ointment base after its preparation. However, further studies are needed in order to more precisely identify the involving mechanisms.
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Background: The neodymium-doped yttrium aluminum garnet (NdYAG) laser therapy has been a popular technique for facial rejuvenation but certain adverse effects like post-infl ammatory hyperpigmentation are issues of concern to Asian patients. Aims: To assess the outcome following combined treatment with vitamin C sonophoresis and NdYAG laser, in selected cases of facial hyperpigmentation. Methods: Twenty three women with dyschromia or melasma who had undergone fi ve sessions of Q-switched NdYAG laser therapy followed by transdermal delivery of vitamin C via sonophoresis were selected after a retrospective review of case records. The objective and subjective clinical outcomes and the side effects, including erythema, scaling, pruritus, dryness and post-infl ammatory hyperpigmentation were evaluated. Results: In both objective or subjective outcomes, 91.3% (21/23) of the patients showed an excellent or better outcome, while 8.7% (2/23) showed no change. A majority of the patients (73.9%, 17/23) experienced no post-infl ammatory hyperpigmentation or had slight post-infl ammatory hyperpigmentation which quickly resolved within 1 week. Only one (4.3%) patient had extreme post-infl ammatory hyperpigmentation which lasted for over a month. Limitations: This was a retrospective study without a control group; a comparative study with a control group (patients treated with the laser alone, without vitamin C sonopheresis) is needed to determine the difference in the outcome. Conclusion: The use of vitamin C sonophoresis along with NdYAG laser may reduce the incidence of adverse effects in Asian patients. Patients experienced obvious improvement in hyperpigmentation and had lower chances of experiencing extreme or severe post-inflammatory hyperpigmentation.
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Sonochemistry is the branch of science which deals with passage of ultrasonic waves to enhance or alter chemical reactions. The use of ultrasound in chemical reactions in solution provides specific activation based on a physical phenomenon: acoustic cavitation. The range from 20 kHz to around 1 MHz is used in sonochemistry whereas frequencies far above 1 MHz are used as medical and diagnostic ultrasound. Ultrasonic waves induce chemical effects on the reaction system, such as generation of free radicals which augment the rate of reaction. Besides this, ultrasound may have other mechanical effects on the reaction system, such as increasing the surface area between the reactants, accelerating dissolution rate. This review elucidates several applications of sonochemistry in the pharmaceutical industry including sonophoresis, sonocrystallization, lowering extraction time, solution atomization and crystallization by sonication, melt sonocrystallization and particle rounding technology. This review also gives an idea about the applications of sonocrystallization in formation of aerosols, enhancing inhalation drug delivery and sonochemical preparation of biomaterials. Its significance in transdermal drug delivery, chemotherapy and cell therapy is also discussed herewith. It has been proved that ultrasound can be effectively used for treatment of sewage sludge and degradation of dangerous chemicals including chlorinated hydrocarbons, aromatic compounds, agrochemicals and pesticides from the agricultural industry, explosives, dyes from the textile industry and surfactants etc. The purpose of this review paper is to put forth the information available in the literature so as to promote further research in the field of sonochemistry.
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Ultrasound is over 20 khz, which represents the upper frequency limit of human hearing. Acoustic vibrations are generated when piezoelectric materials on the thin disc-shaped transducers expand and contract. Although low frequency ultrasound devices have been used widely in the dermatologic area for a long time, the mechanism and side effects have been overlooked. A low-frequency ultrasound device has many benefits on the cosmetic dermatology area by thermal effect, vibration effect, and increase of transdermal delivery of lipophilic drugs or cosmetics. However, there have been reports of dermatitis, dyspnea, dizziness, and burns after treatment with ultrasound. Therefore, the use of this device should be under a doctor's supervision.
Subject(s)
Humans , Acoustics , Burns , Contracts , Cosmetics , Dermatitis , Dermatology , Dizziness , Dyspnea , Hearing , Organization and Administration , Transducers , Ultrasonics , VibrationABSTRACT
An ultrasonic device for medical skin care is used to gently exfoliate the skin of dead skin cells and impurities. Ultrasound waves help loosen and remove oil, dirt and cellular debris from pores. Ponophoresis or sonophoresis is the use of ultrasound to increase percutaneous absorption of drugs, serums, lotions, creams and masques to a depth where it is more effective and beneficial. For improved results and safer procedures, we need to know the contraindications and adverse effects of ultrasonic treatments. Therefore, we summarized and reviewed the issue of safety including contraindications, cautions, and adverse events.
Subject(s)
Skin , Skin Absorption , Skin Care , UltrasonicsABSTRACT
Com o objetivo de avaliar a concentração plasmática de diclofenaco sódico (DS) emulgel em cães com ou sem o uso de fonoforese e de verificar se a fonoforese induz à maior absorção desse fármaco, foram utilizados cinco cães, e todos eles passaram por oito grupos distintos. Um grupo recebeu, via oral, um comprimido de DS, 40mg, por animal, e sete grupos receberam aplicação transdérmica de diclofenaco sódico emulgel por ultrassom. Pela via transdérmica, a área de aplicação era de 20cm². A frequência do ultrassom foi de 1MHz, modo contínuo, com intensidade de 0,4Wcm-2. Colheram-se amostras de sangue antes de se executarem os protocolos - tempo zero -, após uma hora - tempo 1 - e após quatro horas da aplicação - tempo 2 - em todos os grupos, e realizou-se análise das amostras por cromatografia líquida de alta eficiência. Houve diferença (P<0,05) apenas nas amostras no tempo 1 do grupo que recebeu dose oral de DS em relação às outras amostras. Não foi possível verificar concentração plasmática de diclofenaco sódico com aplicação tópica em cães submetidos ou não à fonoforese, apenas quantificou-se o diclofenaco sódico pela administração via oral. A facilitação da penetração transdérmica pelo ultrassom não foi verificada sob o protocolo especificado nesta pesquisa.
The aim of this study was to evaluate the plasma concentration of diclofenac sodium (DS) in dogs submitted to diclofenaco phonophoresis and to evaluate if phonophoresis induces greater absorption of this drug in dogs. Five dogs were used in eight different groups at different times: One group received oral administration of 40mg of DS per dog and seven groups received topical application of emulgel DS. The topical application area was 20cm². A continuous ultrasound frequency of 1MHz and intensity of 0.4W cm-2 was used. Blood collections were performed before the treatment (T0), and 1h (T1) and 4h (T2) after ultrasound application for all groups. DS concentrations in plasma were measured by high performance liquid choramatohraphy (HPLC). There was significant increase of DS plasma concentration only at T1 in the oral administration group. It was not possible to detect any concentration of DS in the plasma of dogs after topical application of DS, even after DS phonophoresis. The facilitation of transdermal penetration by ultrasound has not been verified under the protocol specified in this research.
Subject(s)
Animals , Dogs , Absorption , Absorption/radiation effects , Diclofenac/administration & dosage , Phonophoresis/veterinary , Cell Membrane , Cell Membrane , Administration, Cutaneous , Administration, Oral , Chromatography, High Pressure Liquid/veterinary , UltrasonicsABSTRACT
In this study, various matrix type transdermal patches containing carvedilol of variable combination of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) were prepared by solvent evaporation technique. The patches were prepared by adding surfactant (sodium lauryl sulphate) to promote drug penetration which was found to increase transdermal transport. Therapeutic frequency ultrasound (1 MHz) and surfactant have been individually shown to enhance transdermal drug transport. In this study, we investigated the synergistic effect of ultrasound and surfactants on transdermal drug delivery. This study provides an investigation of the dependence of therapeutic-frequency sonophoresis on various ultrasound parameters, including ultrasound pretreatment time and the distance of the horn from the skin. Based on the in vitro release and in vitro permeation profile the formulation Fs1 (PVP/EC 1:2) shows the best release. Ultrasound was applied to pretreat the skin using a sonicator operating at a frequency of 1 MHz at an intensity 2 Watts/cm2. The optimum ultrasonication time of 50 min at a distance of 1 cm shows the best release. The skin conductivity enhancement was found to be inversely proportional to the distance of horn from the skin and it is directly proportional to ultrasonication pretreatment time. These findings will be useful in optimizing therapeutic-frequency sonophoresis.
ABSTRACT
The transdermal enhancement of ultrasound was discovered 50 years ago.The advantages of low-frequency ultrasound in enhancing the transdermal transport of molecule were discovered in 40 years' study.Because the cavitation is easier to happen in lower frequency ultrasound,the transdermal enhancement of low-frequency ultrasound is higher.The inertial cavitations near the surface of skin play important roles in the transdermal enhancement of low-frequency ultrasound.There are many studies about the effects of the parameters of ultrasound on the transdermal enhancement of low-frequency ultrasound,but there are fewer studies about the effects of other factors.The transdermal enhancement of low-frequency ultrasound has been used for transdermal drug delivery.There are many studies about the transdermal monitoring of glucose and other analytes using low-frequency ultrasound.Many opportunities and challenges lie ahead.