Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,con...Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,conventional MNs employ long needles(≥600μm),leading to pain and skin irritation.Moreover,it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery.Herein,a dually amplified transdermal patch(MN@EV/SC)is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopusinspired suction cup(SC)with short MNs(≤300μm).While leveraging the suction effect to induce nanoscale deformation of the stratum corneum,MN@EV/SC minimizes skin damage and enhances the adhesion of MNs,allowing EV to penetrate deeper into the dermis.When MNs of various lengths are applied to mouse skin,the short MNs can elicit comparable corticosterone release to chemical adhesives,whereas long MNs induce a prompt stress response.MN@EV/SC can achieve a remarkable penetration depth(290μm)for EV,compared to that of MN alone(111μm).Consequently,MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice.Overall,MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.展开更多
The complex skin structure and insufficient intracellular entrapment limit the therapeutic effects of active substances,therefore appealing to a more effective transdermal drug delivery system design.Herein,a hyaluron...The complex skin structure and insufficient intracellular entrapment limit the therapeutic effects of active substances,therefore appealing to a more effective transdermal drug delivery system design.Herein,a hyaluronic acid(HA)modified steareth-2-based niosomes(HA-nio)with satisfactory deformability and targeting properties was designed for ergothioneine(EGT)(EGT@HA-nio)against ultraviolet(UV)-induced skin damage.The unique composition allows EGT@HA-nio to exhibit high mechanical softness,making it deformable to pass through the stratum corneum by the intercellular space without rupture.For further intracellular delivery,HA modification enables EGT to target human dermal cells(HDFs)with increased distribution in mitochondria without the restriction of specific EGT transporter-organic cation transporter1(OCTN-1).Benefiting from the above properties,an adequate amount of EGT in the active form was accumulated in the desired cellular sites,alleviating UV-radiation-induced reactive oxygen species(ROS)generation,inflammatory factor release,DNA damage,and mitochondrial dysfunction.The in vivo experimental results show that EGT@HA-nio could significantly decrease collagen degradation,restore epidermal thickness and morphology to healthy levels,and effectively prevent UV-induced skin damage.With the ability to penetrate biological barriers and deliver drugs,HA-nio may promote the development of inadequate drug penetration disease treatment including skin diseases,cancers,and bacterial infections.展开更多
Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inh...Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inhibits Candida albicans.AmB is primarily administered via oral and intravenous infusion,but severe infusion adverse effects,nephrotoxicity,and potential hepatotoxicity limit its clinical application.Deep eutectic solvents(DESs),with excellent solubilization ability and skin permeability,are attractive for transdermal delivery.Herein,we used DESs to deliver AmB for antifungal therapy transdermally.We first prepared and characterized DESs with different stoichiometric ratios of choline(Ch)and geranate(Ge).DESs increased the solubility of AmB by a thousand-fold.In vitro and in vivo,skin permeation studies indicated that DES_(1:2)(Ch and Ge in 1:2 ratio)had the most outstanding penetration and delivered fluorescence dye to the dermis layer.Then,DES_(1:2)-AmB was prepared and in vitro antifungal tests demonstrated that DES_(1:2)-AmB had superior antifungal effects compared to AmB and DES_(1:2).Furthermore,DES_(1:2)-AmB was skin-irritating and biocompatible.In conclusion,DES-AmB provides a new and effective therapeutic solution for fungal infections.展开更多
Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of tran...Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.展开更多
Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN...Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.展开更多
Objective: Objective: To assess the effect and adverse effects of transdermal fentanyl for elderly patients with cancer pain in China. Methods: A total of 1664 elderly patients (aged 65-90 with mean age of 72.6) with ...Objective: Objective: To assess the effect and adverse effects of transdermal fentanyl for elderly patients with cancer pain in China. Methods: A total of 1664 elderly patients (aged 65-90 with mean age of 72.6) with cancer pain enrolled in the multicenter study from 136 institutes in China. Of them, 408 (28.8%) patients were 75 years old or older. All patients received transdermal fentanyl for the management of cancer pain. The patients were asked to record the attacks of pain, quality of life, and any side effects of the treatment. Results: Baseline mean of pain intensity was 7.34. On day 1, 3, 6, 9 15, and 30, the pain mean scores were decreased to 3.82, 2.80, 2.43, 2.11, 1.83, 1.64 (P=0.000). The effective rate was 97.18%. The mean doses of fentanyl was 31.34 g/h (25-150 g/h) initially, and 40.59 g/h and 47.50 g/h (25-200 g/h) at day 15 and day 30. At treatment day 15, the dose of fentanyl was ranger from 25 to 50 g/h in 91.8% of patients, 75 to 100 g/h in 7.5% patients, and 125 to 200 g/h only in 0.8% patients. The fine quality of life was in 25.4% patients before treatment, and was 71.15% and 73.04% at day 15 and day 30 respectively (P=0.0000). The common side effects were constipation (10.70%), nausea (11.96%), dizzy (6.85%), vomiting (3.85%), sedation (2.40%), Respiratory depression (0.12%). 86.2% patients preferred continue treated by transdermal fentanyl. Conclusions: Transdermal fentanyl for the elderly with cancer pain is effective, safe, convenient, and can improve the quality of life. Transdermal fentanyl can be recommended as a first-line drug for the treatment of elderly patients with moderate to severe cancer pain, and the initial doses is recommended as 25 g/h.展开更多
One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transderm...One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel （DTX）, a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes （SEL） were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application condi- tions. The DTX SELs with optimum composition （phospholipid-surfactant, 85：15, w/w） provided a significantly higher steadystate amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.展开更多
The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the ...The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.展开更多
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 or...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.展开更多
The purpose of this study was to investigate the effects of vehicles and organic acids on the in vitro permeation of letrozole across rat skin. Permeation experiments were carried out with 2-chamber diffusion cells th...The purpose of this study was to investigate the effects of vehicles and organic acids on the in vitro permeation of letrozole across rat skin. Permeation experiments were carried out with 2-chamber diffusion cells through rat skin. The binary solvent mixture of ethanol and isopropyl myristate （IPM） could markedly enhance the cumulative penetrated amount of letrozole after 8 h （Qs） compared with IPM alone, especially the IPM system containing 20% （w/w） ethanol. Surprisingly, the use of complexation with organic acids facilitated skin permeation of letrozole in the IPM--ethanol （20%, w/w） system. Due to different structures of tested organic acids, their effects on the penetration of letrozole were different. This study showed that the addition of an organic acid in the IPM-cthanol （20%, w/w） system was a promising approach to enhance the skin permeability of letrozole.展开更多
Aim To study the influence of electric field direction on the in vitro enhanced transdermal delivery of caffeine by eleetroporation. Methods Using side-by-side compartment diffusion cells method and Ag-Ag/AgCl electro...Aim To study the influence of electric field direction on the in vitro enhanced transdermal delivery of caffeine by eleetroporation. Methods Using side-by-side compartment diffusion cells method and Ag-Ag/AgCl electrodes, the transport of caffeine through human cadaver skin by electroporation （exponentially decaying pulse, pulse voltage = 350 V, pulse frequency = 4 pulses· min^-1, capacity = 22 μF, pulse length = 7 ms, 25 pulses） with different electric field directions was carried out and compared with passive diffusion and iontophoresis （0.25 mA·cm^ - 2, lasted for 4 h）. Results （i） The cumulative quantity and flux of caffeine through human skin were increased significantly by eleetroporation or iontophoresis. （ii） The transport of caffeine by positive iontophoresis （ with electric field from donor to receptor compartment） was significantly greater than that by negative iontophoresis （with electric field from receptor to donor compartment）. （iii） The transport of caffeine by positive eleetroporation （with electric field from donor to receptor compartment） was similar to that by negative eleetroporation （with electric field from receptor to donor compartment）. （iv） The enhancing effect of positive iontophoresis on the transdermal delivery of caffeine was significantly greater than that of electroporation （positive or negative）. Conclusion Electric field direction significantly influences the enhancing effect of iontophoresis on the transdermal delivery of caffeine, but does not influence the enhancing effect of eleetroporation.展开更多
With the development of pharmaceutics and other disciplines theories and advanced technologies, the application of many new drug delivery systems has gradually increased in clinical veterinary. Among the many drug del...With the development of pharmaceutics and other disciplines theories and advanced technologies, the application of many new drug delivery systems has gradually increased in clinical veterinary. Among the many drug delivery systems, transdermal patch can maintain stable and effective plasma concentration and therapeutic effect in vivo for a long time after skin dressing delivery, which provides a safe and effective drug-delivery way for the therapy and prevention of some chronic diseases and partial analgesia in a simple and convenient way. Veterinary drug transdermal preparations have been developed both at home and abroad, and satisfactory results have been achieved in the experimental application. Based on the study of veterinary transdermal patches at home and abroad, this paper systematically describes the development and characteristics of transdermal patches, the factors affecting skin permeation and the evaluation this type of preparations in veterinary drugs.展开更多
Aim Liposomal fluconazole gel was prepared and its properties were studied. Methods The fluconazole liposomes were prepared by film dispersion method. Their shapes and sizes were observed by transmission electronic mi...Aim Liposomal fluconazole gel was prepared and its properties were studied. Methods The fluconazole liposomes were prepared by film dispersion method. Their shapes and sizes were observed by transmission electronic microscope and particle size analyzer, respectively. The skin permeation of liposomal gel was studied on rat skin by permeation cell. Results The entrapment efficiency of flueonazole liposomes was 47.68%. The fluconazole liposomes were oval or round in shape, and their average diameter was 250 ± 8 nm. The accumulative skin permeation of liposomal fluconazole gel （25.27%） was lower than that of non-liposomal fluconazole gel （36.72%）, but fluconazole retained in rat skin of liposomal gel （162 ± 15 μg·cm^-2） was higher than that of nonliposomal gel （48 ± 6μg·cm^-2）. Conclusion Liposomal fluconazole gel can significantly increase the deposited amounts of fluconazole in rat skin and it may be beneficial for topical use.展开更多
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 ...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.展开更多
Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via c...Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Use of traditional physical and chemical enhancers to improve the transdermal permeation rate by increasing drug solubility, diffusion coefficient, and reservoir effect is not feasible owing to the toxic side effects of the overuse of chemical penetration enhancers. Nanoformulations generally vary in size and range from 10 nm to 100 nm. The smaller particle size leads to increased drug permeability, stability, retention, and targeting, making nano-formulations suitable for transdermal drug delivery. The different applications of nano-formulations(vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed.展开更多
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 o...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.展开更多
The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The...The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.展开更多
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...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.展开更多
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 mec...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.展开更多
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 b...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.展开更多
基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSIT)(No.RS-2023-00256265,RS-2024-00352352,RS-2024-00405818)the Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korea government(the Ministry of Science and ICT,the Ministry of Health&Welfare).(No.25A0102L1)support from the Market-led K-sensor technology program(RS-2022-00154781,Development of large-area wafer-level flexible/stretchable hybrid sensor platform technology for form factor-free highly integrated convergence sensor),funded By the Ministry of Trade,Industry&Energy(MOTIE,Korea).
文摘Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,conventional MNs employ long needles(≥600μm),leading to pain and skin irritation.Moreover,it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery.Herein,a dually amplified transdermal patch(MN@EV/SC)is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopusinspired suction cup(SC)with short MNs(≤300μm).While leveraging the suction effect to induce nanoscale deformation of the stratum corneum,MN@EV/SC minimizes skin damage and enhances the adhesion of MNs,allowing EV to penetrate deeper into the dermis.When MNs of various lengths are applied to mouse skin,the short MNs can elicit comparable corticosterone release to chemical adhesives,whereas long MNs induce a prompt stress response.MN@EV/SC can achieve a remarkable penetration depth(290μm)for EV,compared to that of MN alone(111μm).Consequently,MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice.Overall,MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.
基金supported by the National Natural Science Foundation of China(No.82222066)the National Key Research and Development Program of China(No.2022YFC2304104)。
文摘The complex skin structure and insufficient intracellular entrapment limit the therapeutic effects of active substances,therefore appealing to a more effective transdermal drug delivery system design.Herein,a hyaluronic acid(HA)modified steareth-2-based niosomes(HA-nio)with satisfactory deformability and targeting properties was designed for ergothioneine(EGT)(EGT@HA-nio)against ultraviolet(UV)-induced skin damage.The unique composition allows EGT@HA-nio to exhibit high mechanical softness,making it deformable to pass through the stratum corneum by the intercellular space without rupture.For further intracellular delivery,HA modification enables EGT to target human dermal cells(HDFs)with increased distribution in mitochondria without the restriction of specific EGT transporter-organic cation transporter1(OCTN-1).Benefiting from the above properties,an adequate amount of EGT in the active form was accumulated in the desired cellular sites,alleviating UV-radiation-induced reactive oxygen species(ROS)generation,inflammatory factor release,DNA damage,and mitochondrial dysfunction.The in vivo experimental results show that EGT@HA-nio could significantly decrease collagen degradation,restore epidermal thickness and morphology to healthy levels,and effectively prevent UV-induced skin damage.With the ability to penetrate biological barriers and deliver drugs,HA-nio may promote the development of inadequate drug penetration disease treatment including skin diseases,cancers,and bacterial infections.
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi(No.2023010).
文摘Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inhibits Candida albicans.AmB is primarily administered via oral and intravenous infusion,but severe infusion adverse effects,nephrotoxicity,and potential hepatotoxicity limit its clinical application.Deep eutectic solvents(DESs),with excellent solubilization ability and skin permeability,are attractive for transdermal delivery.Herein,we used DESs to deliver AmB for antifungal therapy transdermally.We first prepared and characterized DESs with different stoichiometric ratios of choline(Ch)and geranate(Ge).DESs increased the solubility of AmB by a thousand-fold.In vitro and in vivo,skin permeation studies indicated that DES_(1:2)(Ch and Ge in 1:2 ratio)had the most outstanding penetration and delivered fluorescence dye to the dermis layer.Then,DES_(1:2)-AmB was prepared and in vitro antifungal tests demonstrated that DES_(1:2)-AmB had superior antifungal effects compared to AmB and DES_(1:2).Furthermore,DES_(1:2)-AmB was skin-irritating and biocompatible.In conclusion,DES-AmB provides a new and effective therapeutic solution for fungal infections.
基金supported by the Joint Funds of National Natural Science Foundation of China(No.U22A20162)the Natural Science Foundation of Hebei Province of China(No.C2021202002)+1 种基金the National Natural Science Foundation of China(No.52271245),the Natural Science Foundation of Tianjin(No.21JCQNJC01280)the financial support from the Danish Council for Independent Research(9040-00219B),European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement ENSIGN(Project ID:101086226),L4DNANO(Project ID:101086227).
文摘Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.
文摘Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.
文摘Objective: Objective: To assess the effect and adverse effects of transdermal fentanyl for elderly patients with cancer pain in China. Methods: A total of 1664 elderly patients (aged 65-90 with mean age of 72.6) with cancer pain enrolled in the multicenter study from 136 institutes in China. Of them, 408 (28.8%) patients were 75 years old or older. All patients received transdermal fentanyl for the management of cancer pain. The patients were asked to record the attacks of pain, quality of life, and any side effects of the treatment. Results: Baseline mean of pain intensity was 7.34. On day 1, 3, 6, 9 15, and 30, the pain mean scores were decreased to 3.82, 2.80, 2.43, 2.11, 1.83, 1.64 (P=0.000). The effective rate was 97.18%. The mean doses of fentanyl was 31.34 g/h (25-150 g/h) initially, and 40.59 g/h and 47.50 g/h (25-200 g/h) at day 15 and day 30. At treatment day 15, the dose of fentanyl was ranger from 25 to 50 g/h in 91.8% of patients, 75 to 100 g/h in 7.5% patients, and 125 to 200 g/h only in 0.8% patients. The fine quality of life was in 25.4% patients before treatment, and was 71.15% and 73.04% at day 15 and day 30 respectively (P=0.0000). The common side effects were constipation (10.70%), nausea (11.96%), dizzy (6.85%), vomiting (3.85%), sedation (2.40%), Respiratory depression (0.12%). 86.2% patients preferred continue treated by transdermal fentanyl. Conclusions: Transdermal fentanyl for the elderly with cancer pain is effective, safe, convenient, and can improve the quality of life. Transdermal fentanyl can be recommended as a first-line drug for the treatment of elderly patients with moderate to severe cancer pain, and the initial doses is recommended as 25 g/h.
基金The Key Direction Program of Chinese Academy of Sciences(Grant No.kjcx2-sw-h12-01)
文摘One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel （DTX）, a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes （SEL） were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application condi- tions. The DTX SELs with optimum composition （phospholipid-surfactant, 85：15, w/w） provided a significantly higher steadystate amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.
基金‘863'High Technology R&D Project of Ministry of Science and Technology of China(Grant No.2004AA2Z3073).
文摘The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.
文摘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.
文摘The purpose of this study was to investigate the effects of vehicles and organic acids on the in vitro permeation of letrozole across rat skin. Permeation experiments were carried out with 2-chamber diffusion cells through rat skin. The binary solvent mixture of ethanol and isopropyl myristate （IPM） could markedly enhance the cumulative penetrated amount of letrozole after 8 h （Qs） compared with IPM alone, especially the IPM system containing 20% （w/w） ethanol. Surprisingly, the use of complexation with organic acids facilitated skin permeation of letrozole in the IPM--ethanol （20%, w/w） system. Due to different structures of tested organic acids, their effects on the penetration of letrozole were different. This study showed that the addition of an organic acid in the IPM-cthanol （20%, w/w） system was a promising approach to enhance the skin permeability of letrozole.
文摘Aim To study the influence of electric field direction on the in vitro enhanced transdermal delivery of caffeine by eleetroporation. Methods Using side-by-side compartment diffusion cells method and Ag-Ag/AgCl electrodes, the transport of caffeine through human cadaver skin by electroporation （exponentially decaying pulse, pulse voltage = 350 V, pulse frequency = 4 pulses· min^-1, capacity = 22 μF, pulse length = 7 ms, 25 pulses） with different electric field directions was carried out and compared with passive diffusion and iontophoresis （0.25 mA·cm^ - 2, lasted for 4 h）. Results （i） The cumulative quantity and flux of caffeine through human skin were increased significantly by eleetroporation or iontophoresis. （ii） The transport of caffeine by positive iontophoresis （ with electric field from donor to receptor compartment） was significantly greater than that by negative iontophoresis （with electric field from receptor to donor compartment）. （iii） The transport of caffeine by positive eleetroporation （with electric field from donor to receptor compartment） was similar to that by negative eleetroporation （with electric field from receptor to donor compartment）. （iv） The enhancing effect of positive iontophoresis on the transdermal delivery of caffeine was significantly greater than that of electroporation （positive or negative）. Conclusion Electric field direction significantly influences the enhancing effect of iontophoresis on the transdermal delivery of caffeine, but does not influence the enhancing effect of eleetroporation.
基金Supported by the Program for Technology Research and Development and Its Demonstration and Popularization of Beijing Vocational College of Agriculture(XY-YF-15-08)~~
文摘With the development of pharmaceutics and other disciplines theories and advanced technologies, the application of many new drug delivery systems has gradually increased in clinical veterinary. Among the many drug delivery systems, transdermal patch can maintain stable and effective plasma concentration and therapeutic effect in vivo for a long time after skin dressing delivery, which provides a safe and effective drug-delivery way for the therapy and prevention of some chronic diseases and partial analgesia in a simple and convenient way. Veterinary drug transdermal preparations have been developed both at home and abroad, and satisfactory results have been achieved in the experimental application. Based on the study of veterinary transdermal patches at home and abroad, this paper systematically describes the development and characteristics of transdermal patches, the factors affecting skin permeation and the evaluation this type of preparations in veterinary drugs.
文摘Aim Liposomal fluconazole gel was prepared and its properties were studied. Methods The fluconazole liposomes were prepared by film dispersion method. Their shapes and sizes were observed by transmission electronic microscope and particle size analyzer, respectively. The skin permeation of liposomal gel was studied on rat skin by permeation cell. Results The entrapment efficiency of flueonazole liposomes was 47.68%. The fluconazole liposomes were oval or round in shape, and their average diameter was 250 ± 8 nm. The accumulative skin permeation of liposomal fluconazole gel （25.27%） was lower than that of non-liposomal fluconazole gel （36.72%）, but fluconazole retained in rat skin of liposomal gel （162 ± 15 μg·cm^-2） was higher than that of nonliposomal gel （48 ± 6μg·cm^-2）. Conclusion Liposomal fluconazole gel can significantly increase the deposited amounts of fluconazole in rat skin and it may be beneficial for topical use.
文摘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.
基金supported by the Postdoctoral Innovation Talents Support Program(No.BX20180207)the National Nature Science Foundation of China(No.81502722)
文摘Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Use of traditional physical and chemical enhancers to improve the transdermal permeation rate by increasing drug solubility, diffusion coefficient, and reservoir effect is not feasible owing to the toxic side effects of the overuse of chemical penetration enhancers. Nanoformulations generally vary in size and range from 10 nm to 100 nm. The smaller particle size leads to increased drug permeability, stability, retention, and targeting, making nano-formulations suitable for transdermal drug delivery. The different applications of nano-formulations(vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed.
基金supported by the National Natural Science Foundation of China(No.51873194)the Natural Science Foundation of Zhejiang Province,China(No.LY18E030006).
文摘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.
基金supported by the National Natural Science Foundation of China(No.81073059)the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.
基金Supported by of the "863" Program of China(No 2003AA2Z347C)
文摘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.
文摘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.
文摘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.
