Transdermal Penetration Enhancers Research Articles

Research model integrating "both medicinal and adjuvant properties" for essential oils from Chinese medicinal: based on characterization of medicinal properties

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.

Investigation of muscone as transdermal penetration enhancer: Enhancing activity and molecular mechanisms

The aim of this present study was to investigate the enhancing activities of animal-derived muscone on the transdermal permeation of drugs with different lipophilicities and shed light on its possible mechanisms of action. The epidermal keratinocytes and dermal fibroblast cell lines were employed to evaluate the cytotoxicity of muscone using MTT assay. A series of model drugs with a wide range of lipophilicity were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were used. The saturation solubilities and SC/vehicle partition coefficients of model drugs were measured to monitor the effect of muscone on drug thermodynamic activities and partition of drug into SC layer, respectively. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and Raman spectroscopy were used to understand the effect of muscone on molecular organization of the stratum corneum (SC). It was found that muscone displayed lower cytotoxicity than the commonly-used and standard penetration enhancer Azone. Meanwhile, muscone could significantly promote the percutaneous absorption of all of five model drugs. The molecular mechanism studies revealed that muscone could enhance the skin permeability predominantly by interacting with the SC lipids, especially the disorder of the lipid bilayer packing. These results suggested that muscone could be a safe and efficient penetration enhancer in the external use.

Potential of Sonophoresis as a Skin Penetration Technique in the Treatment of Rheumatoid Arthritis with Transdermal Patch.

Rheumatoid arthritis, a chronic disorder, limits the use of chemical penetration enhancers for a prolonged period of time. Moreover, systemic routes of administration of the first-line drug, methotrexate, have shown undesirable systemic as well as local side effects. The objective of this research was to overcome the limitations associated with treatment of rheumatoid arthritis by utilizing three physical transdermal penetration enhancement techniques namely cold-laser, electroporation, and sonophoresis to deliver methotrexate. Methotrexate patch was prepared using solvent casting method and the ex-vivo release of methotrexate in combination with three physical penetration enhancers (sonophoresis, electroporation, and cold laser) were studied. The best technique was employed in pre-clinical testing in arthritic and control groups of male Wistar rats excluding remaining two techniques. The comparative ex-vivo studies showed that the penetration enhancement of methotrexate is maximum by sonophoresis followed by electroporation and cold laser (sonophoresis > electroporation > cold laser). In pharmacodynamic studies, the reduction in diameter of injected and non-injected paw on day 5 and day 21 for group 4 (ultrasound pre-treated group) was higher as compared to group 3 (group receiving only methotrexate patch). The motility score and the reduction in pain were significantly improved for group 4 than group 3 on both day 5 and day 21 (P˂0.05) which confirmed the faster recovery of animals of group 4 due to penetration enhancement of methotrexate patch by ultrasound treatment. From the results, it can be concluded that sonophoresis along with methotrexate patch has shown a significant effect in the treatment of rheumatoid arthritis.

New zwitterionic HP-β-CD-PEI-MPC polymer used as a transdermal penetration enhancer

In this study, a new kind of zwitterionic hydroxypropyl-β-cyclodextrin-polyethyleneimine grafted 2-methylallyloxyethyl phosphorylcholine (HP-β-CD-PEI1800-MPC) transdermal penetration enhancer was successfully synthesized, and its feasibility for promoting transdermal absorption of the hydrophilic drug Vitamin B12 was evaluated. The enhancer was synthesized by epoxy ring-opening and the Michael addition reaction, and its structure was confirmed by nuclear magnetic resonance spectrum (1HNMR). The penetration enhancing effect of HP-β-CD-PEI1800-MPC on hydrophilic vitamin B12 was evaluated by transdermal experience in vitro. A skin irritation experiment and histopathological observations of skin sections with hematoxylin and eosin (H&E) and Masson staining were performed to analyze the safety of HP-β-CD-PEI1800-MPC. A preliminary study was conducted on the promoting mechanism of the transdermal enhancer using laser Raman spectroscopy, ATR-FTIR and DSC. The transdermal depth and distribution of the enhancer in skin were examined by fluorescence labeling. In vitro transdermal permeation was determined by Franz cells, and the cumulative drug content through skin was measured by HPLC. All the data showed that HP-β-CD-PEI1800-MPC could be a safe and effective penetration enhancer for topical drug delivery.

Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, HSL and HMG-CoA reductase in hyperlipidemia rabbits

To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits. Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone IIA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05). The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Mechanisms of white mustard seed (Sinapis alba L.) volatile oils as transdermal penetration enhancers

We investigated the transdermal drug permeation enhancement properties and associated mechanisms of white mustard (Sinapis alba L.) seed volatile oil (SVO). Using gas chromatography–mass spectrometry, we showed that SVO was composed primarily of allylisothiocyanate and isothiocyanatocyclopropane. Compared with azone, SVO had better penetration-enhancing effects on three model drugs (5-Fluorouracil, Osthole, and Paeonol), with each having different oil-water partition coefficients. Histopathology showed that SVO did not induce skin irritation when the concentration was lower than 2% (v/v), and it induced less irritation than azone. According to attenuated total reflection-Fourier transform infrared spectroscopy and transmission electron microscopy, SVO induced skin lipid structural disorder and increased the distance between the stratum corneum, which is beneficial to the penetration of drugs. Cellular experiments showed that SVO inhibited Ca2+-ATPase activity, increased intracellular Ca2+ concentration, and changed the membrane potential in HaCaT cells, which promoted drug transfer into the skin. Our findings reveal that SVO is a safe and efficient natural product that has great potential as skin penetration enhancer.

Percutaneous Delivery Application of Acylated Steric Acid-9-P(arginine) Cell Penetrating Peptides Used as Transdermal Penetration Enhancer++

In this study, a cell-penetrating peptide named Acylated Steric acid-9 poly-arginine (r9-SA) was sucessfully synthesized. High performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to characterize the structural formula of r9-SA. Diclofenac sodium was chosen as a model drug, and the transdermal permeation-enhancing effect of r9-SA was estimated in vitro. Skin irritation experiment and histopathological observation of tissue sections with HE and Masson staining were performed to analyze the security of r9-SA. The possible penetration-enhancing mechanism of r9-SA was characterized with laser scanning confocal microscopy (LSCM), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and laser Raman spectroscopy, respectively. The in vitro penetration study showed that r9-SA has a promoting effect for enhancing the transdermal penetration of diclofenac sodium. Skin irritation experiment and histopathological observation results showed that r9-SA has good biocompatibility with skin. The experiments were carried on to characterize the penetration mechanism of r9 -SA. It was found that r9-SA may react with the keratin in the stratum corneum (SC), changing its secondary structure and so that drugs can penetrate through SC. In conclusion, all data showed that the r9-SA could be a safe and effective penetration enhancer for topical delivery of drug.

Skin Electrical Resistance Measurement of Oxygen-Containing Terpenes as Penetration Enhancers: Role of Stratum Corneum Lipids.

The measurement of skin electrical resistance (SER) has drawn a great deal of attention for the rapid screening of transdermal penetration enhancers (PEs). However, the mechanisms underlying the SER measurement are still unclear. This study was to investigate the effects and mechanisms of seven oxygen-containing terpenes on the SER kinetics. Stratum corneum (SC) lipids were proved to play a key role in SER measurement. Then, the factors affecting the SER measurement were optimized. By the determination of SER kinetics, cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol and α-terpineol) were demonstrated to possess higher enhancement ratio (ER) values compared with linear terpenes (linalool, geraniol and citral). For the first time, the linear correlation was found between ER of terpenes and the interaction energy of terpene–ceramide complexes revealed by molecular simulation. The attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis revealed that the effect of cyclic terpenes on SC lipid arrangement was obviously stronger than that of linear terpenes. In addition, by evaluating HaCaT skin cell viability, little difference was found between the toxicities of cyclic and linear terpenes. In conclusion, measurement of SER could be a feasible approach for the efficient evaluation of the PEs that mainly act on SC lipids.

An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright ‘Franz-type’ diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

Diclofenac in the treatment of pain in patients with rheumatic diseases.

Diclofenac, a phenylacetic acid derivative, is a drug demonstrating high efficacy after oral administration in the treatment of pain and physical disability in rheumatic diseases. In view of the adverse effects associated with using diclofenac, it is necessary to consider all known drug safety information before the drug is selected for therapy and the dosage regimen is set for individual patients. Selecting an oral dosage form with specific properties determined by excipients is a method to improve the availability of the drug substance and, at the same time, minimize adverse drug reactions. An alternative to tablet or capsule dosage forms is diclofenac application to the skin. The proven efficacy of this method is further improved through the use of transdermal penetration enhancers and vehicle ingredients which provide dosage forms with specific physical properties.

Cytotoxicity and penetration enhancement activity of essential oils from warming the interior medicinals with hot or warm property in terms of Traditional Chinese Medicine

OBJECTIVETo investigate on the cytotoxicity and penetration enhancement effect of essential oils (EOs) from warming the interior medicinals (WIM) from Traditional Chinese Medicine (TCM). METHODSEOs were extracted from WIM of Bichengqie (Litseae Fructus), Dingxiang (Flos Syzygii Aromatici), Huajiao (Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang (Fructus Foeniculi) with warm nature, and Ganjiang (Rhizoma Zingiberis), Gaoliangjiang (Rhizoma Alpiniae Officinari), Rougui (Cortex Cinnamomi Cassiae), and Wuzhuyu (Fructus Evodiae Rutaecarpae) with hot nature, respectively. Their chemical compositions were analyzed by gas chromatography-mass spectrometry (GC-MS). The cytotoxicity of the extracted eight EOs on HaCaT cells was measured and compared. Moreover, analyses of cell cycle and cell apoptosis were performed to investigate the cytotoxic mechanism. The transdermal penetration enhancement effects of the extracted eight EOs on ibuprofen were further compared by the modified Franz diffusion cell method. RESULTSThe most abundant constituents in the extracted eight EOs were determined to be monoterpenes, especially oxygen-containing monoterpenes. The HaCaT cell cytotoxicity of EOs from WIM with hot nature were significantly (P = 0.020) higher than that with warm nature. Both ginger oil and zanthoxylum oil significantly induced G0/G1 phase arrestment in HaCaT cell cycle. For ginger oil from WIM with hot nature and zanthoxylum oil from WIM with warm nature, the main mechanisms of the cytotoxicity were found to be the induction of cellular necrosis and the cellular apoptosis, respectively. Furthermore, most of the tested EOs showed remarkable penetration enhancement activity on ibuprofen. However, no statistical significance (P = 0.18) was found between penetration enhancement activity of EOs from WIM with warm nature and EOs from WIM with hot nature. CONCLUSIONWith the enhanced penetration activity, the extracted EOs from the WIM demonstrated their significant effect of the cytotoxicity on the skin cells.

Effect of the Dispersion States of Azone in Hydroalcoholic Gels on Its Transdermal Permeation Enhancement Efficacy

The objective of this study was to investigate the effect of dispersion states of azone in gels on the transdermal permeation of levamisole hydrochloride (LH). LH hydroalcoholic gels containing azone of different dispersion states were prepared by varying the contents of azone and Tween 80, and the in vitro transdermal permeation of LH across excised rat skin was evaluated. Depending on the content of azone, mixed solvents, and solubilizer used, azone presented as dissolved molecules, solubilized in micelles, and fine or coarse emulsion droplets in gels. Dramatically increased transdermal permeation of LH within the azone contents between 0.25% and 0.75% indicated high transdermal enhancement efficiency of the molecular or micellar azone, and extra azone that existed as oil droplets did not fully exert transdermal penetration enhancement of LH. Although solubilizer (Tween 80) can greatly increase the solubility of azone, only small amount of Tween 80 (0.5%) in the gel significantly increased the steady-state flux of LH. Addition of extra amount of Tween 80 (>0.5%) reduced the amount of azone distributed in the skin, and thus decreased the transdermal drug permeation. The results partly elucidated the versatile effects of the dispersion states of azone on the transdermal permeation of hydrophilic drug from semisolid gels.

In vivo transdermal penetration enhancing activity of essential oil from Zanthoxyli Pericarpium by using microdialysis technique

The aim of this paper is to investigate the topical pharmacodynamics behavior of different lipophilic model drugs after treatment with essential oil from Zanthoxyli Pericarpium by using the cutaneous microdialysis technique, and then evaluate its in vivo transdermal penetration enhancing properties. Two traditional Chinese medicine active components, namely tetramethylpyrazine and puerarin, were chosen as lipophilic and hydrophilic model drugs, respectively. Firstly, the concentration difference method was employed to measure the in vitro recovery rate and loss of the microdialysis probe, and the in vivo recoveries of two model drugs were determined by using the retrodialysis method. Secondly, the skin pharmacodynamics behaviors of two model drugs were studied after treatment with different concentrations of the essential oil, and the well-established and standard penetration enhancer Azone was selected as a positive control. It was found that the recovery of microdialysis probe was equal to its loss for two model drugs, with no interaction between drugs in dialysis membranes. The retrodialysis studies revealed that the in vivo recovery of tetramethylpyrazine and puerarin were 59.17%, 19.85%, respectively. The skin pharmacodynamics studies showed that the essential oil could facilitate the transdermal absorption of tetramethylpyrazine in a concentration-dependent manner, and the enhancement ratio (ER) for 5% essential oil was 98.64, which was higher than that of the optimum concentration of Azone (3% Azone, ER=89.11). Meanwhile, the Zanthoxyli Pericarpium could effectively promote the transdermal permeation of the puerarin in a concentration-dependent manner. Hence, this study further confirmed that the Zanthoxyli Pericarpium had excellent penetration-enhancing activity as a natural transdermal penetration enhancer, providing data support for its application in traditional Chinese medicine external preparations.

Effect of wintergreen oil on in vitro transdermal permeation of osthole and geniposide

The aim of this study was to investigate the transdermal penetration enhancement effect of wintergreen oil and its action mechanisms. The in vitro transdermal tests were carried out to study the transdermal penetration enhancement effect of wintergreen oil by using osthole and geniposide as the lipophilic and hydriphilic model drugs. Fourier-transform infrared spectroscopy was used to investigate the effect of wintergreen oil on the molecular structure of rat stratum corneum, and the scanning electron microscope was employed to observe the change of rat skin surface after treatment by the oil. The wintergreen oil at proper concentrations could effectively promote the transdermal permeation of osthole and geniposide, and exhibited better penetration-enhancing activity for the lipophilic osthole, close to the commonly used classical penetration enhancer azone. The infrared spectroscopy study and scanning electron microscope showed that wintergreen oil mainly acted on the stratum corneum lipids, reduced dense stratum corneum, and reduced the skin barrier function. Thus, the wintergreen oil could effectively facilitate the transdermal absorption of the lipophilic and hydrophilic drugs, resulting from the lowed skin barrier function.

The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

Background: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu’s cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. Methods: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC0–t, AUMC0–t), area under the zero and first moment curves from 0 to infinity (AUC0–∞, AUMC0–∞), maximum plasma concentration (Cmax) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. Results: In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with the control group, the indomethacin skin percutaneous rate of the FCT low-intensity group (FCTL) was 35.52%, and the enhancement ratio (ER) at 9 h was 1.76X, roughly equivalent to the penetration enhancing effect of the CPEs and iontophoresis. Secondly, the indomethacin percutaneous ratio of the FCT middle-intensity group (FCTM) and FCT high-intensity group (FCTH) were 47.36% and 54.58%, respectively, while the ERs at 9 h were 3.58X and 8.39X, respectively. Thirdly, pharmacokinetic data showed that in vivo indomethacin percutaneous absorption of the FCT was much higher than that of the control, that of the FCTM was slightly higher than that of the CPE, and that of the FCTM group was significantly higher than all others. Meanwhile, variance analysis indicated that the combination of the FCT penetration enhancement method and the CPE method had beneficial effects in enhancing skin penetration: the significance level of the CPE method was 0.0004, which was lower than 0.001, meaning the difference was markedly significant; the significance level of the FCT was also below 0.0001 and its difference markedly significant. The significance level of factor interaction A × B was lower than 0.0001, indicating that the difference in synergism was markedly significant. Moreover, SEM and TEM images showed that the SC surfaces of Sprague-Dawley rats treated with FCT were damaged, and it was difficult to observe the complete surface structure, with SC pores growing larger and its special “brick structure” becoming looser. This indicated that the barrier function of the skin was broken, thus revealing a potentially major route of skin penetration. Conclusion: FCT, as a new form of transdermal penetration technology, has significant penetration effects with TCM characteristics and is of high clinical value. It is worth promoting its development.

Influence of Temperature on Transdermal Penetration Enhancing Mechanism of Borneol: A Multi-Scale Study.

The influence of temperature on the transdermal permeation enhancing mechanism of borneol (BO) was investigated using a multi-scale method, containing a coarse-grained molecular dynamic (CG-MD) simulation, an in vitro permeation experiment, and a transmission electron microscope (TEM) study. The results showed that BO has the potential to be used as a transdermal penetration enhancer to help osthole (OST) penetrate into the bilayer. With the increasing temperature, the stratum corneum (SC) becomes more flexible, proving to be synergistic with the permeation enhancement of BO, and the lag time (TLag) of BO and OST are shortened. However, when the temperature increased too much, with the effect of BO, the structure of SC was destroyed; for example, a water pore was formed and the micelle reversed. Though there were a number of drugs coming into the SC, the normal bilayer structure was absent. In addition, through comparing the simulation, in vitro experiment, and TEM study, we concluded that the computer simulation provided some visually detailed information, and the method plays an important role in related studies of permeation.

Investigation of the Efficacy of Transdermal Penetration Enhancers Through the Use of Human Skin and a Skin Mimic Artificial Membrane

The aim of this study was to investigate the behavior of promising penetration enhancers through the use of 2 different skin test systems. Hydrogel-based transdermal formulations were developed with ibuprofen as a nonsteroidal anti-inflammatory drug. Transcutol and sucrose esters were used as biocompatible penetration enhancers. The permeability measurements were performed with ex vivo Franz diffusion cell methods and a newly developed Skin Parallel Artificial Membrane Permeability Assays (PAMPA) model. Franz diffusion measurement is commonly used as a research tool in studies of diffusion through synthetic membranes in vitro or penetration through ex vivo human skin, whereas Skin PAMPA involves recently published artificial membrane-based technology for the fast prediction of skin penetration. It is a 96-well plate-based model with optimized artificial membrane structure containing free fatty acid, cholesterol, and synthetic ceramide analog compounds to mimic the stratum corneum barrier function. Transdermal preparations containing 2.64% of different sucrose esters and/or Transcutol and a constant (5%) of ibuprofen were investigated to determine the effects of these penetration enhancers. The study demonstrated the good correlation of the permeability data obtained through use of human skin membrane and the in vitro Skin PAMPA system. The Skin PAMPA artificial membrane serves as quick and relatively deep tool in the early stages of transdermal delivery systems, through which the enhancing efficacy of excipients can be screened so as to facilitate the choice of effective penetration components.

Essential Fatty Acids as Transdermal Penetration Enhancers

The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid™ technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid™ delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F >> control > EPO >> Pheroid™. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum–epidermis and the epidermis–dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid™ formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation.

Nanotechnology approaches for pain therapy through transdermal drug delivery.

The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.

Simple amides of oleanolic acid as effective penetration enhancers.

Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented.