Analysis of efficacy and safety of preventive analgesia with transdermal therapeutic system Duragesic Matrix in spine surgery

The survey studies analgesic effect of postoperative therapy in two groups of patients with spinal disorders. In the first group the standard scheme with NSAID on demand was used. In the second group transdermal therapeutic system Duragesic Matrix was applied. The pain level (by pain level scale) as well as psychological status and IL-6 rate (a reliable indicator of surgical trauma and pain severity) were assessed before and after surgery. Transdermal therapeutic system Duragesic Matrix applied before surgery appeared to be more effective for analgesic therapy than standard scheme with NSAID on demand.     

神经外科开颅术后患者疼痛及控制状况的调查

目的调查神经外科开颅手术患者术后疼痛及控制状况,为术后镇痛治疗提供依据。方法选择北京天坛医院神经外科开颅手术患者100例,采用疼痛视觉模拟评分（VAS）、Ramsay镇静评分于术后2h和24h评估患者意识和疼痛状况,并进行术后疼痛调查问卷,记录不良事件。结果本组患者术后均使用静脉镇痛泵。术后2h无痛38例（38％）,轻度疼痛49例（49％）,中度疼痛12例（12％）,重度疼痛1例（1％）;术后24h无痛24例（24％）,轻度疼痛30例（30％）,中度疼痛36例（36％）,重度疼痛10例（10％）。结论神经外科开颅手术患者术后存在不同程度的疼痛,术后镇痛需要进一步深化。     

Ultrasound-mediated transdermal drug delivery: Mechanisms, scope, and emerging trends

The use of ultrasound for the delivery of drugs to, or through, the skin is commonly known as sonophoresis or phonophoresis. The use of therapeutic and high frequencies of ultrasound (≥ 0.7 MHz) for sonophoresis (HFS) dates back to as early as the 1950s, while low-frequency sonophoresis (LFS, 20-100 kHz) has only been investigated significantly during the past two decades. Although HFS and LFS are similar because they both utilize ultrasound to increase the skin penetration of permeants, the mechanisms associated with each physical enhancer are different. Specifically, the location of cavitation and the extent to which each process can increase skin permeability are quite dissimilar. Although the applications of both technologies are different, they each have strengths that could allow them to improve current methods of local, regional, and systemic drug delivery. In this review, we will discuss the mechanisms associated with both HFS and LFS, specifically concentrating on the key mechanistic differences between these two skin treatment methods. Background on the relevant physics associated with ultrasound transmitted through aqueous media will also be discussed, along with implications of these phenomena on sonophoresis. Finally, a thorough review of the literature is included, dating back to the first published reports of sonophoresis, including a discussion of emerging trends in the field.     

Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery.

To overcome the skin's barrier properties that block transdermal delivery of most drugs, arrays of microscopic needles have been microfabricated primarily out of silicon or metal. This study addresses microneedles made of biocompatible and biodegradable polymers, which are expected to improve safety and manufacturability. To make biodegradable polymer microneedles with sharp tips, micro-electromechanical masking and etching were adapted to produce beveled- and chisel-tip microneedles and a new fabrication method was developed to produce tapered-cone microneedles using an in situ lens-based lithographic approach. To replicate microfabricated master structures, PDMS micromolds were generated and a novel vacuum-based method was developed to fill the molds with polylactic acid, polyglycolic acid, and their co-polymers. Mechanical testing of the resulting needles measured the force at which needles broke during axial loading and found that this failure force increased with Young's modulus of the material and needle base diameter and decreased with needle length. Failure forces were generally much larger than the forces needed to insert microneedles into skin, indicating that biodegradable polymers can have satisfactory mechanical properties for microneedles. Finally, arrays of polymer microneedles were shown to increase permeability of human cadaver skin to a low-molecular weight tracer, calcein, and a macromolecular protein, bovine serum albumin, by up to three orders of magnitude. Altogether, these results indicate that biodegradable polymer microneedles can be fabricated with an appropriate geometry and sufficient strength to insert into skin, and thereby dramatically increase transdermal transport of molecules.     

Hydrogen-bond super-amphiphile based drug delivery system: design,synthesis, and biological evaluation

Drug delivery systems (DDSs) show great application prospects in tumor therapy. So far, physical encapsulation and covalent grafting were the two most common strategies for the construction of DDSs. However, physical encapsulation-based DDSs usually suffered from low drug loading capacity and poor stability, and covalent grafting-based DDSs might reduce the activity of original drug, which greatly limited their clinical application. Therefore, it is of great research value to design a new DDS with high drug loading capacity, robust stability, and original drug activity. Herein, we report a super-amphiphile based drug delivery system (HBS-DDS) through self-assembly induced by hydrogen bonds between amino-substituted N-heterocycles of the 1,3,5-triazines and hydrophilic carmofur (HCFU). The resulting HBS-DDS had a high drug loading capacity (38.1%) and robust stability. In addition, the drug delivery system exhibited pH-triggered size change and release of drugs because of the pH responsiveness of hydrogen bonds. In particular, the anticancer ability test showed that the HBS-DDS could be efficiently ingested by tumor cells, and its half-maximal inhibitory concentration (IC₅₀ = 3.53 μg mL⁻¹) for HeLa cells was close to that of free HCFU (IC₅₀ = 5.54 μg mL⁻¹). The hydrogen bond-based DDS represents a potential drug delivery system in tumor therapy.

Drug delivery systems (DDSs) show great application prospects in tumor therapy.     

Comparative evaluation of methods of analgesia after operations on the stomach

A general somatic syndromal approach to evaluation of clinical status by SAPS II and APACH II scores was used in 41 patients operated on for gastric cancer. Epidural analgesia in these patients promoted rapid regression of the severity of condition, did not require high opioid doses, had a positive effect on the peristaltic activity of the intestine, and accelerated treatment in intensive care wards.     

Mode of delivery following labor epidural analgesia: influence of ropivacaine and bupivacaine.

Epidural analgesia is a popular and effective method for pain relief during labor. Bupivacaine is a commonly used local anesthetic for labor epidural analgesia. Ropivacaine is an amino acid local anesthetic that is structurally related to bupivacaine with a similar potency and duration, but ropivacaine has less cardiac toxicity than bupivacaine and produces less motor blockade. These properties make ropivacaine a desirable local anesthetic agent for obstetrical analgesia. The purpose of the present study was to compare the cesarean section and instrumental delivery rates for patients receiving labor epidural analgesia using bupivacaine and ropivacaine. The medical records of 500 consecutive patients receiving bupivacaine for labor epidural analgesia were reviewed. After a 3-month familiarization period for ropivacaine, the records of 500 consecutive patients receiving ropivacaine for labor epidural analgesia similarly were reviewed. The groups did not differ demographically. The instrumental delivery rate was 14.2% for the bupivacaine group and 9.8% for the ropivacaine group. The cesarean section rate was 14% for the bupivacaine group and 10.2% for the ropivacaine group. At our facility, the use of ropivacaine decreased both cesarean section and instrumental delivery rates when compared with bupivacaine in the population studied.     

复合芬太尼与罗哌卡因用于临产分娩镇痛的对照研究

[目的]探讨芬太尼与罗哌卡因自控镇痛用于分娩镇痛的对照研究。[方法]采用回顾性分析的方法,选择200例健康、单胎、足月临产初产妇,观察组(100例)采用0.1%罗哌卡因 芬太尼(1μg/mL)硬膜外腔给药用于分娩镇痛,对照组(100例)未实施任何镇痛措施。观察两组产妇的镇痛效果、产程时间、分娩方式、新生儿Αpgar评分及产后24h出血量。[结果]镇痛有效率为96.0%;两组产妇在产程中血压、脉搏、呼吸的变化差异无统计学意义(P>0.05);产程时间比较:第一产程和总产程差异有统计学意义(P<0.05),第二产程、第三产程差异无统计学意义(P>0.05);分娩方式及缩宫素使用情况比较:观察组缩宫素使用明显多于对照组,差异有统计学意义(P<0.05);剖宫产率比较差异有统计学意义(P<0.05);新生儿Αpgar评分及产后24h出血量两组比较差异均无统计学意义(P>0.05)。[结论]低浓度的罗哌卡因复合芬太尼用于分娩镇痛对产妇第一产程及总产程有缩短作用,降低剖宫产率,自控镇痛,同时增加了缩宫素使用率,但对新生儿出生结局无明显影响。     

NMR characterisation and transdermal drug delivery potential of microemulsion systems.

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.     

Gelatin-stabilised microemulsion-based organogels: rheology and application in iontophoretic transdermal drug delivery

Gelatin-containing microemulsion-based organogels (MBGs) have been formulated using pharmaceutically acceptable surfactants and oils such as Tween 85 and isopropyl myristate. MBG formulations were subject to rheological study and their utility in transdermal drug delivery examined. Unlike most organogels, MBGs are electrically conducting and have been successfully employed in this study for the iontophoretic delivery of a model drug through excised pig skin. Iontophoresis using MBGs gave substantially higher release rates for sodium salicylate compared to passive diffusion, and fluxes were proportional to the drug loading and the current density. MBGs provide a convenient means of immobilising the drug and are rheologically similar to their hydrogel counterparts at comparable gelatin concentrations. MBGs also appear to offer improved microbial resistance in comparison to aqueous solution or hydrogels.     

复合芬太尼与罗哌卡因用于临产分娩镇痛的对照研究

[目的]探讨芬太尼与罗哌卡因自控镇痛用于分娩镇痛的对照研究.[方法]采用回顾性分析的方法,选择200例健康、单胎、足月临产初产妇,观察组(100例)采用0.1%罗哌卡因 芬太尼(1μg/mL)硬膜外腔给药用于分娩镇痛,对照组(100例)未实施任何镇痛措施.观察两组产妇的镇痛效果、产程时间、分娩方式、新生儿Apgar评分及产后24 h出血量.[结果]镇痛有效率为96.0%;两组产妇在产程中血压、脉搏、呼吸的变化差异无统计学意义(P＞0.05);产程时间比较:第一产程和总产程差异有统计学意义(P＜0.05),第二产程、第三产程差异无统计学意义(P＞0.05);分娩方式及缩宫素使用情况比较:观察组缩宫素使用明显多于对照组,差异有统计学意义(P＜0.05);剖宫产率比较差异有统计学意义(P＜0.05);新生儿Apgar评分及产后24 h出血量两组比较差异均无统计学意义(P＞0.05).[结论]低浓度的罗哌卡因复合芬太尼用于分娩镇痛对产妇第一产程及总产程有缩短作用,降低剖宫产率,自控镇痛,同时增加了缩宫素使用率,但对新生儿出生结局无明显影响.     

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin can be controlled. Furthermore, the newly developed monitoring system provides a tool for rapid real-time determination of both, transdermal and topical delivery, when the delivered molecule is fluorescent.     

Hemodynamic characteristics in preeclampsia women during cesarean delivery after spinal anesthesia with ropivacaine

BACKGROUND Very few studies have been published on the hemodynamic changes associated with spinal anesthesia induced with ropivacaine during cesarean deliveries in preeclamptic women.AIM To record and analyze hemodynamic data in women with preeclampsia undergoing cesarean delivery after spinal anesthesia induced with ropivacaine.METHODS Ten eligible women with preeclampsia were enrolled in this prospective observational study.Spinal anesthesia was performed with 2.4 mL of 0.5%ropivacaine.Hemodynamic changes were then analyzed at multiple time points.The hemodynamic responses to vasopressor interventions and uterotonic agents,as well as maternal and neonatal outcomes were also recorded.RESULTS Stable hemodynamic trends were observed in this study.Cardiac output(CO)and stroke volume increased mildly during surgery.In contrast,mean arterial pressure and systemic vascular resistance showed a moderate decrease from induction until the end of surgery.Central venous pressure dramatically increased after delivery.Oxytocin administration was associated with the most significant hemodynamic fluctuations during surgery,namely,an increase in CO and heart rate.Phenylephrine intervention was only required in three patients,and caused an increase in mean arterial pressure and systemic vascular resistance along with a decrease in heart rate,stroke volume,and CO.No maternal and neonatal complications were observed during this study,except transient episodes of hypotension.CONCLUSION Spinal anesthesia for caesarian delivery with ropivacaine in women with preeclampsia is linked to modest hemodynamic changes of no clinical significance in this study.Careful cardiovascular monitoring is still recommended,particularly after the delivery of the fetus or the use of oxytocin.     

Controlled drug release from a novel liposomal delivery system. I. Investigation of transdermal potential

The in vitro release behavior of a novel liposome-based drug delivery device has been characterized. The system consists of a molded agarose matrix in which the model drug (progesterone) was dispersed either free or associated with one of four lipid formulations: egg-phosphatidylcholine (EPC) liposomes, EPC/cholesterol (2:1) liposomes, Intralipid^® emulsion, and dipalmitoylphosphatidylcholine (DPPC) liposomes. Drug release rates from the devices into aqueous buffer were measured at 37° C. The free progesterone release rate decreased rapidly over 24 h with over 90% delivered. The liposomal patches, on the other hand, imposed apparent zero-order kinetics: for example, both the EPC and DPPC systems delivered their progesterone payloads at about 1%/h over 24 h. Further, the EPC and DPPC patches significantly slowed transdermal drug delivery across excised hairless mouse skin. The EPC device retarded throughput to one-half the control value, the DPPC system reduced the transport kinetics by an order of magnitude. The results support two hypotheses: (a) the liposomal-based reservoir system can modulate drug input via the skin, (b) the zero-order release of progesterone from liposomes is determined by slow interfacial transport out of the bilayer into the surrounding aqueous medium.     

Optimization of iontophoretic transdermal delivery of a peptide and a non-peptide drug

In vitro iontophoretic transdermal delivery (ITD) of a tripeptide, enalaprilat (EP) and a non-peptide, cromolyn sodium (CS), across frozen hairless guinea pig (HGP) skin were investigated. Parameters for optimization of ITD included the influence of ionic strength (μ), buffer type and size, drug loading in the donor and the effect of pH. Drug permeation into the receptor compartment was monitored using HPLC assay methods developed for the study. An optimum μ of 6.66 mM in acetate buffer was found necessary for efficient ITD of CS. An exponential decrease in the flux of CS was observed with an increasing μ. Buffer ions larger than acetate ions inhibited the transport of CS ions. With an increase in the donor concentration of CS, a hyperbolic relationship for the increase in flux was observed. For EP, permeation was not detectable when μ was increased to greater than 31 mM in phosphate-buffered solution. With an increase in pH above the pK_a1 (3.55) for EP, a linear decrease in flux was observed. Higher drug loading of EP in the donor compartment provided better permeation. Effect of freezing of HGP skin on the iontophoretic delivery of EP and CS was also evaluated. Flux values for either of the drugs studied were similar when frozen or fresh skins were used. Reversibility studies indicated that no gross current induced permeation changes occurred with the HGP skin. Passive permeation of either of the drugs investigated was negligible.     

Control of drug concentration-time profiles in vivo by zero-order transdermal delivery systems

Control of 9-β-arabinofuranosyladenine (ara-A) and ara-A-2',3'-diacetate (ara-ADA) concentrations in blood from zero-order transdermal delivery systems was achieved using newly designed transdermal patches with rate-limiting membranes. Membrane permeability coefficients were altered by changing copolymer compositions of 2-hydroxyethyl methacrylate (HEMA) with styrene (St) or N-vinylpyrrolidone (VP). The copolymers compositions were chosen according to the hydration properties of the membrane.In vitro permeability coefficients of 5 × 10⁻⁶, 1 × 10⁻⁶, 5 × 10⁻⁷and 1 × 10⁻⁷ cm/s were obtained for ara-A and ara-ADA with the membranes used in the transdermal patches. In vivo blood levels of the total drug (i.e., drug plus metabolites) were monitored following application of the patch on Azone pretreated abdominal sites of hairless mice. The drug concentration-time profiles agreed with the values predicted from the theoretical model developed from the in vitro studies.     

中药经皮给药治疗仪在小儿高热中的应用

摘要:[目的]寻求简便易行、容易被患儿接受的物理加药物降温方法.[方法]对136例高热患儿在给予常规治疗(抗感染、对症)的基础上加用中药经皮给药治疗仪治疗.[结果]患儿体温在30 min～60 min能够缓解和降至正常,有效率为100%.[结论]中药经皮给药治疗仪治疗小儿高热疗效确切.     

ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug

The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin.OCIS codes: (170.3880) Medical and biological imaging, (300.6540) Spectroscopy, ultraviolet, (120.7280) Vibration analysis, (300.6340) Spectroscopy, infrared, (300.6300) Spectroscopy, Fourier transforms, (170.5660) Raman spectroscopy