The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch

Chronic pain lasting more than 3 mo,or even several years can lead to disability.Treating chronic pain safely and effectively is a critical challenge faced by clinicians.Because administration of analgesics through oral,intravenous or intramuscular routes is not satisfactory,research toward percutaneous delivery has gained interest.The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area.It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery,which reduces the dose frequency and side effects.If not required,then the patch can be removed from the skin immediately.The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979.From then on,the transdermal patch has been widely used to treat many diseases.To date,no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery.The pain branch of the Chinese Medical Association,after meeting and discussing with experts and based on clinical evidence,developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

Transdermal drug delivery systems in diabetes management: A review

Diabetes mellitus is a chronic disease in which there is an insufficient production of insulin by the pancreas, or the insulin produced is unable to be utilized effectively by the body. Diabetes affects more than 415 million people globally and is estimated to strike about 642 million people in 2040. The WHO reported that diabetes will become the seventh biggest cause of mortality in 2030. Insulin injection and oral hypoglycemic agents remain the primary treatments in diabetes management. These often present with poor patient compliance. However, over the last decade, transdermal systems in diabetes management have gained increasing attention and emerged as a potential hope in diabetes management owing to the advantages that they offer as compared to invasive injection and oral dosage forms. This review presents the recent advances and developments in transdermal research to achieve better diabetes management. Different technologies and approaches have been explored and applied to the transdermal systems to optimize diabetes management. Studies have shown that these transdermal systems demonstrate higher bioavailability compared to oral administration due to the avoidance of first-pass hepatic metabolism and a sustained drug release pattern. Besides that, transdermal systems have the advantage of reducing dosing frequency as drugs are released at a predetermined rate and control blood glucose level over a prolonged time, contributing to better patient compliance. In summary, the transdermal system is a field worth exploring due to its significant advantages over oral route in administration of antidiabetic drugs and biosensing of blood glucose level to ensure better clinical outcomes in diabetes management.

Physicochemical Properties and Evaluation of Microemulsion Systems for Transdermal Delivery of Meloxicam

Microemulsion systems, composed of water, isopropyl myristate （IPM）, polyoxyethylene sorbitan trioleate （Tween 85 ）, and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug（ meloxicam）. The purpose of this study was to investigate the physicochemieal properties of the tested microemulsion and to find the correlation between the physicoehemical properties and the skin permeation rate of the microemulsion. Pseudo-ternary phase diagram of the investigated system at a constant surfactant/cosurfactant mass ratio （ Km = 1 ： 1 ） was constructed by titration at 20℃, and the five fommlations were selected for further research in the o/w microemulsion domains. The values of electrical conductivity and viscosity showed that the selected systems were bicontinuous or non-spherical o/w microemulsion, and the electrical conductivity and viscosity were increased with increasing the content of water. These results suggest that the optimum formulation of microemulsion, containing 0. 375 meloxicam, 5% isopropyl myristate, 25% Tween 85. 25% ethanol, and water, showed the maximum permeation rate. It had a high electrical conductivity, small droplet size, and proper viscocity.

Investigating the potential of essential oils as penetration enhancer for transdermal losartan delivery: Effectiveness and mechanism of action

The effect of tea tree oil(TTO),cumin oil(CO),rose oil(RO)and aloe vera oil(AVO)on the skin permeation of losartan potassium(LP)was investigated.In vitro skin permeation studies were carried out using rat skin.The mechanism of skin permeation enhancement of LP by essential oils treatment was evaluated by FTIR,DSC,activation energy measurement and histopathological examination.Both concurrent ethanol/enhancer treatment and neat enhancer pretreatment of rat SC with all the oils produced significance increase in the LP flux over the control.The effectiveness of the oils as the penetration enhancers was found to be in the following descending order:AVO>RO>CO>TTO.However,only AVO was the only enhancer to provide target flux required to deliver the therapeutic transdermal dose of LP.FTIR and DSC spectra of the enhancer treated SC indicated that TTO,CO,RO and AVO increased the LP permeation by extraction of SC lipids.The results of thermodynamic studies and histopathological examination of AVO treated SC suggested additional mechanisms for AVO facilitated permeation i.e.transient reduction in barrier resistance of SC and intracellular transport by dekeratinization of corneocytes which may be attributed to the presence of triglycerides as constituents of AVO.It is feasible to deliver therapeutically effective dose of LP via transdermal route using AVO as penetration enhancer.

Fabrication of gelatin methacryloyl hydrogel microneedles for transdermal delivery of metformin in diabetic rats

Injection therapy for diabetes has poor patient compliance,and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients.In this work,to demonstrate the benefits of an alternative drug delivery technique that overcomes these issues,methacrylated gelatin hydrogel-forming microneedles integrated with metformin were developed to adjust blood glucose levels in diabetic rats.Gelatin methacryloyl microneedles(GelMA-MNs)with different degrees of substitution were successfully prepared by a micro-molding method.The resultant GelMA-MNs exhibited excellent mechanical properties and moisture resistance.Metformin,an anti-diabetic drug,was further encapsulated into the GelMA-MNs,and its release rate could be controlled by the three-dimensional cross-linked network of microneedles,thereby exhibiting sustained drug release behaviors in vitro and implying a better therapeutic effect compared with that of subcutaneous injection in diabetic rats.The drug release period could be significantly prolonged by improving the cross-link density of GelMA-MNs.The results of hypoglycemic effect evaluation show that the application of GelMA-MNs for transdermal delivery in diabetic rats has promising benefits for diabetes treatment.

Multicenter Clinical Study for Evaluation of Efficacy and Safety of Transdermal Fentanyl Matrix Patch in Treatment of Moderate to Severe Cancer Pain in 474 Chinese Cancer Patients

Objective: Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. Methods: A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 ?g/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days. Results: After 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63?1.26 to 2.03?1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001). Conclusion: The new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.

Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation

Meloxicam(MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acidbase neutralization. With poloxamer 407 and Tween 80(80/20, w/w) as mixed stabilizers,MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However, the nanoprecipitation process reduced the crystallinity of MLX.Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58-and 4.4-fold increase in AUC0 →2 4 h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.

Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice

Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional recovery.We hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve injury.Mice with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP dose.While a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle controls.These findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal degeneration.The animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on March 31,2017.

Pharmacokinetics of Two Ingredients of the Compound Chinese Herbal Medicine Transdermal Preparation in Cows

The topical administration of the compound Chinese herbal medicine transdermal preparation has been widely used in treating the mastitis of cows. In order to understand the metabolic process, four cows suffering from clinical mastitis were selected for the pharmacokinetic study. The transdermal preparation was applied to the diseased part of breast. Then the plasma and milk samples were collected respectively at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 36 h, The concentrations of baicalin and phillyrin in plasma and milk were determined by HPLC and the data of time-concentrations were analyzed by the pharmacokinetic software. The results showed that two ingredients in the plasma were not detectable, but they in the milk had linear relationship with the time. The peak concentration of baicalin [（2.84 ±0.15）μg mL^-1] appeared at （4.93 ± 0.35） h, AUC0.1OQ was （27.32 ± 7.91） mg L^-1 h^-1, and the mean retention time was （28.31 ±0.49） h. The peak concentration of phillyrin [（0.49 ± 0.41） μg mL^-1] achieved at （3.68 ± 3.14） h, AUC0-LOQ was （4.10± 0.31） mg L^-1 h^-1, and the mean retention time was （14.52 ± 0.02） h. These suggested that two ingredients had slow absorbing speed and high absorbing degree. They could not be eliminated in a short time, thus exerted the topical curative effect.

Transdermal permeation of Zanthoxylum bungeanum essential oil on TCM components with different lipophilicity

Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Methods:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin.Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z.bungeanum oil.The molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action.Results:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs.After treatment with Z.bungeanum oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration increased.There was no significant difference between the control and the Z.bungeanum oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased.The oxygen-containing constituents in Z.bungeanum oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide 3.Conclusion:Z.bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic drugs.The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient,saturation solubility,and the interactions with SC lipids.

Novel chemical permeation enhancers for transdermal drug delivery

Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However,development of transdermal products is primarily hindered by the low permeability of the skin.To overcome this barrier effect,numerous new chemicals have been synthesized as potential permeation enhancers for transdermal drug delivery.In this review,we presented an overview of the investigations in this field,and further implications on selection or design of suitable permeation enhancers for transdermal drug delivery were also discussed.

Effect of backing films on the transdermal delivery of cyclobenzaprine patch

The aim of this study was to investigate the effect of backing films on transdermal delivery of cyclobenzaprine patch. Different backing films were chosen to prepare the cyclobenzaprine transdermal patch. The cumulative amount of cyclobenzaprine released from different patches was evaluated in vitro. To investigate the interaction between cyclobenzaprine and backing films, the partitioning experiments and attenuated total reflectance Fourier transform infrared(ATR-FTIR) spectroscopy were performed. The cumulative amount of cyclobenzaprine released from the patch with Cotran? 9700 as backing film was less than that of other patches with different backing films. Furthermore, the cumulative amount of cyclobenzaprine released from the patch with Cotran? 9700 as backing film decreased significantly after 7 d storage at room condition. The partitioning experiments indicated a strong adsorption of cyclobenzaprine onto the Cotran? 9700, which could explain the decrease of cumulative amount of cyclobenzaprine released from the patch with Cotran? 9700 as backing film. According to the ATR-FTIR results, there was no interaction between Cotran? 9700 and cyclobenzaprine. The effect of backing films on the release behavior of cyclobenzaprine transdermal patch was attributed to the adsorption of cyclobenzaprine onto the Cotran? 9700.

Investigation of Microemulsion System for Transdermal Drug Delivery of Amphotericin B

In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl alcohol and water for transdermal delivery of AraB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conductivities（σ）. The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into microemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature（PIT） of the emulsifier obtains the maximum drug content（2.96 mg/mL）. The pH value of the system could be adjusted to pH〉8.5 or pH〈5.2, in this range AraB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1：1, O/SC 1：9（mass ratio of oil phase to surfactant/cosurfactant blend）, water content 64.6%, drug content （2.93±0.08） mg/mL, showed the maximum permeation rate （3.255 ±0.64） μg·cm^-2.h^-1 which is stable for a long time.

Evaluation of blank film forming polymeric dispersions based on Eudragit RL 30D and RS30D for transdermal drug delivery

The first approved transdermal drug delivery system in the United States in 1979 is a scopolamine patch for treatment of motion sickness. Transdermal drug delivery system has many advantages over oral route such as it is useful for vomiting and unconscious patients. It can avoid first pass metabolism by the liver. It is non-invasive way and self-administered system compared to injections. The film forming polymeric solutions are a novel transdermal drug delivery system. This system consists of an active drug, film forming polymer, plasticizer.

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Transdermal drug delivery （TDD） can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid （HA） in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers （e.g., their penetration depth and concentration） could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents （UCAs）. When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 p.m. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 p.m, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications （e.g., nanoparticle drug carriers, transdermal patches and cosmetics）, protocols and methods presented in this paper are potentially useful.

Transdermal delivery of fluorescein isothiocyanate-dextrans using the combination of microneedles and low-frequency sonophoresis

This study aimed to evaluate the patient-friendly methods that are used in the delivery of hydrophilic macromolecules into deep skin layers,in particular,the combination of microneedles patch(MNs patch)and low-frequency sonophoresis(SN).The hydrophilic macromolecule drug fluorescein isothiocyanate(FITC)-dextrans(FD-4:MW 4.4 kDa)was used as the model drug in our experimental design.In this study,excised porcine skin was used to investigate and optimize the key parameters that determine effective MNs-and SNfacilitated FD-4 delivery.In vitro skin permeation experiments revealed that the combination of MNs patch with SN had a superior enhancing effect of skin permeation for FD-4 compared to MNs alone,SN alone or untreated skin,respectively.The optimal parameters for the combination of MNs and SN included the following:10 N insertion force of MNs,4 W/cm^(2)SN intensity,6 mm radiation diameter of the SN probe,2 min application time,and the continuous mode duty cycle of SN.In addition,vertical sections of skin,clearly observed under a confocal microscope,confirmed that the combination of MNs and SN enhanced permeation of FD-4 into the deep skin layers.These studies suggest that the combination of MNs and SN techniques could have great potential in the delivery of hydrophilic macromolecules into deep skin.

Efficacy and Safety of Transdermal Fentanyl(TDF)in Treatment of Pain Caused by Interventional Embolization Therapy

Objective： Interventional embolization therapy is well accepted in cancer treatment, but patient may suffer from a moderate-to-severe pain after therapy and its quality of life （QoL） is influenced, this study is to observe the efficacy and safety of transdermal fentanyl （TDF） in the management of pain caused by interventional embolization therapy. Methods： Morphine 10mg and TDF 25μg/h were immediately used in 52 patients who had moderate-to-severe pain complicated by interventional embolization therapy, the pain intensity was evaluated by visual analogue scale （VAS）. If VAS≥4 at t2 h after treatment, the dosage of TDF added into 50 μg/h. At 0h, 12h, 24h, 72h, 1 week, 2 weeks after TD, the vas and adverse events were observed respectively. Result： There was an obvious decrease in VAS at 12h after TDF treatment in the patients of which only 9 patients used 50ug/h dosage after partial splenic embolization （PSE） therapy. Most patients got satisfactory pain relief both the TDF 25 μg/h and TDF 50 μg/h group （VAS 0-1）. The adverse events were nausea, vomiting and dizzy, especially in the TDF 50 μg/h group. No respiratory depression was observed and only one patient got retention of urine. Conclusion： TDF was effective and safe in the treatment of moderate-to-severe pain after interventional embolizafion therapy.