Mechanism Of Penetration Enhancement Research Articles

The bottomhole stress field analysis and the rate of penetration enhancement mechanism of a new type of central-grooved single-cone/multi-blade hybrid bit for deep well drilling

In this work, a high efficiency rock-breaking idea of forming an isolated rock column in the center of the deep bottomhole, that is, a convex-stepped bottomhole and a new type of central-grooved single-cone/multi-blade hybrid bit (CSMHB) are proposed due to the problems of poor drillability of rock, low efficiency of rock breaking at the center of bit and low rate of penetration (ROP) in the deep hard formation drilling. Based on the poroelasticity theory, a numerical simulation model of the stress field of convex-stepped bottomhole is established, and the dynamic changes of the stress field of convex-stepped bottomhole with time are analyzed. Meanwhile the rock strength failure of the convex-stepped bottomhole under the stress field is analyzed based on the three-dimensional Coulomb criterion, which preliminarily reveals the ROP enhancement mechanism of the CSMHB. The research shows that after the convex-stepped bottomhole is opened, the convex area of the bottomhole is subjected to tensile stress in the circumferential, radial and axial directions. In the bottomhole area broke by PDC cutting structure, the part near the central rock column is also subjected to tensile stress in the circumferential, radial and axial directions, while the other area is subjected to compressive stress. The action range of tensile stress and the damage range of the central rock column at the bottomhole expand with the increase of the indent length and diameter of the single-cone bit respectively. The average effective stress and damage function at the center of bottomhole decrease with the increase of the indent length and diameter of the single-cone bit respectively.

Mechanisms of Penetration Enhancement and Transport Utilizing Skin Keratine Liposomes for the Topical Delivery of Licochalcone A.

Keratin liposomes have emerged as a useful topical drug delivery system given theirenhanced ability to penetrate the skin, making them ideal as topical drug vehicles. However, the mechanisms of the drug penetration enhancement of keratin liposomes have not been clearly elucidated. Therefore, licochalcone A(LA)-loaded skin keratin liposomes (LALs) were prepared to investigate their mechanisms of penetration enhancement on the skin and inB16F10 cells. Skin deposition studies, differential scanning calorimetry (DSC), attenuated total reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and skin distribution and intracellular distribution studies were carried out to demonstrate the drug enhancement mechanisms of LALs. We found that the optimal application of LALs enhanced drug permeation via alterations in the components, structure, and thermodynamic properties of the stratum corneum (SC), that is, by enhancing the lipid fluidization, altering the skin keratin, and changing the thermodynamic properties of the SC. Moreover, hair follicles were the main penetration pathways for the LA delivery, which occurred in a time-dependent manner. In the B16F10 cells, the skin keratin liposomes effectively delivered LA into the cytoplasm without cytotoxicity. Thus, LAL nanoparticles are promising topical drug delivery systems for pharmaceutical and cosmetic applications.

Topical delivery of gambogic acid assisted by the combination of low-frequency ultrasound and chemical enhancers for chemotherapy of cutaneous melanoma

Anti-cutaneous melanoma activity of the skin-delivered gambogic acid (GA) has been reported in our previous study. However, it is difficult for GA to diffuse passively through intact skin without any enhancement means. In this study, a combination of chemical enhancers (EN: azone and propylene glycol) and physical ultrasound (US) was used to improve the percutaneous permeation of GA and enhance the anti-melanoma activity. The enhancement effect of the combination of EN and US (EN-US) on GA in vitro and in vivo was studied, and the enhancement mechanism and skin irritation were also evaluated. We showed that the parameters of US application at a constant frequency (30 kHz) with a duty cycle of 100% and intensity of 1.75 W/cm2 for 20 min were optimal. In vitro, EN-US showed a considerable enhancement of the permeation of GA, and the enhancement effect was stronger than that with the use of EN or US alone. In vivo antitumor study showed that the tumor growth was significantly inhibited after percutaneous administration of GA by EN-US, more than in the intravenous injection group. The penetration enhancement mechanism revealed that EN-US not only altered the structure of lipid bilayers and keratins to reduce the barrier effect of the stratum corneum but also produced diffusion channels in the skin under the cavitation effect of US, thereby promoting the skin penetration of GA. In addition, there was no observable skin irritation in mice after treatment with EN-US. Our study demonstrated that the combination of EN and US improved the skin permeation and retention of GA to enhance the anti-melanoma activity. This method also provides technical guidance for the future development of topical and transdermal therapeutic system of GA.

In-vitro evaluation of meloxicam permeation using response surface methodology

The influences of combination of different mechanisms of penetration enhancers (such as azone, sodium lauryl sulfate and menthol) on the percutaneous absorption of meloxicam formulations throughh rat skin were investigated using uniform deign and response surface methodology. The uniform design was applied to prepare systematic model formulations which were composed of three formulation factors: Azone (x1), sodium lauryl sulfate (x2), and menthol (x3). The result showed that azone had the highest potential influence on the penetration absorption of meloxicam, followed by sodium lauryl sulfate and menthol. With zero-order delivery, the required flux of meloxicam gel to maintain a therapeutic concentration was about 400 μg/hr/cm2. The result showed that the optimal addition concentration of azone at 4% to 6% could be obtained at high penetration rate and short lag time of meloxicam gel. It was shown that as the concentration of sodium lauryl sulfate increased from 0% to 12% the flux and cumulative amount at 48 hr increased and lag time decreased. On the other hand, menthol had the effect of a shorter lag time. To validate the predictive ability of the hypothesized model, the predicted formulations were prepared and penetration experiments were performed. The predicted formulations were developed for the transdermal drug delivery system.

A multiscale study of the penetration-enhancing mechanism of menthol

Abstract Objective Transdermal drug delivery systems represent a critical focus in the pharmaceutics field; however, their use is limited by the fact that many drugs usually pass through the skin with low permeability. Menthol is a common penetration enhancer because of its high penetration-enhancing efficiency and safety. Our research aimed to reveal the penetration-enhancing mechanisms of menthol via a multiscale study. Methods First, the interaction of menthol with the stratum corneum was studied using vertical Franz diffusion cells obtained from the abdominal skin of rats as a model. Then, the skin samples were observed via transmission electron microscopy. Finally, the interaction of different concentrations of menthol with a mixed lipid model of the stratum corneum was investigated via molecular dynamics simulation using the GROMOS 54A7 force field on a microcosmic level. Results At concentrations of 3.5% or lower, menthol changed the original structure of the stratum corneum to varying degrees, which increased its fluidity and facilitated the permeation and storage of menthol. Menthol increased the fluidity of the stratum corneum mainly via two mechanisms. First, menthol had strong hydrogen-bonding capability, and it could compete for the lipid–lipid hydrogen bonding sites, thereby weakening the stability of the hydrogen-bonding network connecting the skin lipids. In addition, menthol had strong affinity for cholesterol, probably due to their similar molecular structures, suggesting that the incorporation of menthol would increase the fluidity of the lipid membrane similarly to cholesterol. Conclusion The penetration-enhancing mechanism of menthol was explained using in vitro and molecular dynamics simulation methods. These findings may advance the basic research of transdermal drug delivery systems and facilitate the discoveries of novel penetration enhancers.

Application of PTFE/Al Reactive Materials for Double-Layered Liner Shaped Charge.

The penetration enhancement behaviors of a reactive material double-layered liner (RM-DLL) shaped charge against thick steel targets are investigated. The RM-DLL comprises an inner copper liner, coupled with an outer PTFE (polytetrafluoroethylene)/Al reactive material liner, fabricated via a cold pressing/sintering process. This RM-DLL shaped charge presents a novel defeat mechanism that incorporates the penetration capability of a precursor copper jet and the chemical energy release of a follow-thru reactive material penetrator. Experimental results showed that, compared with the single reactive liner shaped charge jet, a deeper penetration depth was produced by the reactive material-copper jet, whereas the penetration performance and reactive material mass entering the penetrated target strongly depended on the reactive liner thickness and standoff. To further illustrate the penetration enhancement mechanism, numerical simulations based on AUTODYN-2D code were conducted. Numerical results indicated that, with increasing reactive liner thickness, the initiation delay time of the reactive materials increased significantly, which caused the penetration depth and the follow-thru reactive material mass to increase for a given standoff. This new RM-DLL shaped charge configuration provides an extremely efficient method to enhance the penetration damage to various potential targets, such as armored fighting vehicles, naval vessels, and concrete targets.

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.

Lipid nanoparticles loading triptolide for transdermal delivery: mechanisms of penetration enhancement and transport properties

BackgroundIn recent years, nanoparticles (NPs) including nanostructured lipid carries (NLC) and solid lipid nanoparticles (SLN) captured an increasing amount of attention in the field of transdermal drug delivery system. However, the mechanisms of penetration enhancement and transdermal transport properties of NPs are not fully understood. Therefore, this work applied different platforms to evaluate the interactions between skin and NPs loading triptolide (TPL, TPL-NLC and TPL-SLN). Besides, NPs labeled with fluorescence probe were tracked after administration to investigate the dynamic penetration process in skin and skin cells. In addition, ELISA assay was applied to verify the in vitro anti-inflammatory effect of TPL-NPs.ResultsCompared with the control group, TPL-NPs could disorder skin structure, increase keratin enthalpy and reduce the SC infrared absorption peak area. Besides, the work found that NPs labeled with fluorescence probe accumulated in hair follicles and distributed throughout the skin after 1 h of administration and were taken into HaCaT cells cytoplasm by transcytosis. Additionally, TPL-NLC could effectively inhibit the expression of IL-4, IL-6, IL-8, IFN-γ, and MCP-1 in HaCaT cells, while TPL-SLN and TPL solution can only inhibit the expression of IL-6.ConclusionsTPL-NLC and TPL-SLN could penetrate into skin in a time-dependent manner and the penetration is done by changing the structure, thermodynamic properties and components of the SC. Furthermore, the significant anti-inflammatory effect of TPL-NPs indicated that nanoparticles containing NLC and SLN could serve as safe prospective agents for transdermal drug delivery system.

Elucidation of penetration enhancement mechanism of Emu oil using FTIR microspectroscopy at EMIRA laboratory of SESAME synchrotron

It has been proposed that Emu oil possesses skin permeation-enhancing effect. This study aimed to address its possible penetration enhancement mechanism(s) using IR microscopy, in accordance with LPP theory. The penetration of Emu oil through the layers of human skin was accomplished by monitoring oil-IR characteristic feature at 3006cm−1. The unsaturated components of Emu oil accumulated at about 270μm depth of skin surface. The interaction of Emu oil with lipid and protein constituents of SC was investigated in comparison with a commonly used enhancer, IPM. Inter-sample spectral differences were identified using PCA and linked with possible enhancement mechanisms. Emu oil treatment caused a change in the slope of the right contour of amide I band of the protein spectral range. This was also clear in the second derivative spectra where the emergence of a new shoulder at higher frequency was evident, suggesting disorganization of keratin α-helix structure. This effect could be a result of disruption of some hydrogen bonds in which amide CO and NH groups of keratin are involved. The low intensity of the emerged shoulder is also in agreement with formation of weaker hydrogen bonds. IPM did not affect the protein component. No conclusions regarding the effect of penetration enhancers on the SC lipids were obtained. This was due to the overlap of the endogenous (skin) and exogenous (oil) CH stretching and scissoring frequencies. The SC carbonyl stretching peak disappeared as a result of IPM treatment which may reflect some degree of lipid extraction.

Fatty acids penetration into human skin ex vivo: A TOF-SIMS analysis approach.

Linoleic, oleic, palmitoleic, palmitic, and stearic fatty acids (FAs) are commonly used in dermatological formulations. They differ by their structure, presence in the skin, and mode of application in pharmaceuticals and cosmetics compounding. These FAs are also known as chemical penetration enhancers, but their mechanisms of penetration enhancement and effect on barrier characteristics of the skin require additional study. In this study, the authors conducted an ex vivo analysis of the distribution of lipid components in the epidermis and dermis of human skin after applying individual FAs. The goal was to elucidate possible mechanisms of penetration enhancement and FA effects on barrier characteristics of the skin. FA penetration studies were conducted ex vivo on human skin and time-of-flight secondary ion mass spectrometry (TOF-SIMS) bioimaging analysis was performed to visualize and analyze distribution of FAs in skin sections. The current study demonstrated that TOF-SIMS imaging was effective in visualizing the distribution of linoleic, oleic, palmitoleic, palmitic, and stearic acid in the human skin ex vivo after the skin penetration experiment of individual FAs. The integration of the obtained TOF-SIMS images allowed a semiquantitative comparison of the effects induced by individual FA applications on the human skin ex vivo. FAs showed varying abilities to penetrate the skin and disorder the FAs within the skin, based on their structures and physicochemical properties. Linoleic acid penetrated the skin and changed the distribution of all the analyzed FAs. Skin treatment with palmitoleic or oleic acid increased the amounts of singular FAs in the skin. Penetration of saturated FAs was low, but it increased the detected amounts of linoleic acid in both skin layers. The results indicate that application of FAs on the skin surface induce redistribution of native FAs not only in the stratum corneum layer of epidermis but also in the lipid content of full epidermis and dermis layers. The results indicate that topically applied pharmaceutical products should be evaluated for potential chemical penetration enhancement and lipid component redistribution effects during formulation.

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.

Development of essential oils as skin permeation enhancers: penetration enhancement effect and mechanism of action

Context: Essential oils (EOs) have shown the potential to reversibly overcome the stratum corneum (SC) barrier to enhance the skin permeation of drugs. Objective: The effectiveness of turpentine, Angelica, chuanxiong, Cyperus, cinnamon, and clove oils were investigated for the capacity and mechanism to promote skin penetration of ibuprofen. Materials and methods: Skin permeation studies of ibuprofen across rat abdominal skin with the presence of 3% w/v EOs were carried out; samples were withdrawn from the receptor compartment at 8, 10, 22, 24, 26, 28, 32, 36, and 48 h and analyzed for ibuprofen content by the HPLC method. The mechanisms of penetration enhancement of EOs were further evaluated by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis and determination of the properties of EOs. Moreover, the toxicities of EOs on skin cells were also measured. Results: The enhancement ratio (ER) values of turpentine, Angelica, chuanxiong, Cyperus, cinnamon, clove oils and azone were determined to be 2.23, 1.83, 2.60, 2.49, 2.63 and 1.97, respectively. Revealed by ATR-FTIR analysis, a linear relationship (r = 0.9045) was found between the ER values and the total of the shift of peak position of SC lipids. Furthermore, the results of HaCaT skin cell toxicity evaluation revealed that the natural EOs possessed relatively lower skin irritation potential. Conclusion: Compared with azone, the investigated EOs possess significantly higher penetration enhancement effect and lower skin toxicity. EOs can promote the skin permeation of ibuprofen mainly by disturbing rather than extracting the SC lipids.

Sucrose esters as biocompatible surfactants for penetration enhancement: An insight into the mechanism of penetration enhancement studied using stratumcorneum model lipids and Langmuir monolayers

Up to now, the molecular mechanism of the penetration enhancing effect of sucrose esters (SEs) on stratumcorneum (SC) has not been explained in details. In this study, variety of surface sensitive techniques, including surface pressure-area (π-A) isotherms, infrared reflection-absorption spectroscopy (IRRAS), and Brewster angle microscopy (BAM), have been used to investigate interactions between SEs and SC intercellular lipids. A monolayer of the mixture of ceramide AS C18:18, stearic acid and cholesterol in the molar ratio of 1:1:0.7 on an aqueous subphase is a good model to mimic a single layer of intercellular SC lipids. The π-A isotherms of mixed monolayers and parameters derived from the curves demonstrated the interaction between nonionic surfactants such as SEs and SC lipids. With increasing SE concentration, the resultant monolayer films became more fluid and better compressible. IRRAS measurements showed that SEs disordered the acyl chains of SC lipids, and the BAM images demonstrated the modification of the domain structures in SC monolayers. Longer chain-SE has a stronger disordering effect and is better miscible with ceramides in comparison to SE with a shorter hydrophobic part. In conclusion, this study demonstrates the disordering effect of SEs on the biomimetic SC model, pointing out that small changes in the structure of surfactant may have a strong influence on a penetration enhancement of lipophilic drugs through intercellular lipids of skin.

A Multiscale Study on the Penetration Enhancement Mechanism of Menthol to Osthole.

Menthol is a widely used penetration enhancer in clinical medicine due to its high efficiency and relative safety. However, details of the penetration enhancement mechanism of menthol on the molecular level is rarely involved in the discussion. In this work, the penetration enhancement (PE) mechanism of menthol is explored by a multiscale method containing molecular dynamics simulations, in vitro penetration experiments, and transmission electron microscopy. Osthole is chosen to be the tested drug due to its common use in external preparations and because it often accompanies menthol as a PE in the preparations. The results show that menthol in each testing concentration can impair the lipid packing of stratum corneum (SC) and promote osthole permeating into SC, and the penetration promoting effect has an optimal concentration. At a low concentration, menthol causes the bilayer to relax with a reduction in thickness and increment in the lipid headgroup area. At a high concentration, menthol destroys the bilayer structure of SC and causes lipids to form a reversed micelle structure. The penetration enhancement mechanism of menthol is characterized mainly by the disruption of the highly ordered SC lipid in low concentrations and an improvement in the partitioning of drugs into the SC in high concentrations. The results can provide some assistance for additional studies and applications of menthol as a penetration enhancer.

Correlation between the chemical composition of thermoresponsive nanogels and their interaction with the skin barrier

In this paper we present a comprehensive study for the ability of thermoresponsive nanogels (tNG) to act as cutaneous penetration enhancers. Given the unique properties of such molecular architectures with regard to their chemical composition and thermoresponsive properties, we propose a particular mode of penetration enhancement mechanism, i.e. hydration of the stratum corneum. Different tNG were fabricated using dendritic polyglycerol as a multifunctional crosslinker and three different kinds of thermoresponsive polymers as linear counterpart: poly(N-isopropylacrylamide) (pNIPAM), p(di(ethylene glycol) methyl ether methacrylate - co - oligo ethylene glycol methacrylate) (DEGMA-co-OEGMA475), and poly(glycidyl methyl ether - co - ethyl glycidyl ether) (tPG). Excised human skin was investigated by means of fluorescence microscopy, which enabled the detection of significant increment in the penetration of tNG as well as the encapsulated fluorescein. The morphology of the treated skin samples was thoroughly investigated by transmission electron microscopy and stimulated Raman spectromicroscopy. We found that tNG can perturbate the organization of both proteins and lipids in the skin barrier, which was attributed to tNG hydration effects. Interestingly, different drug delivery properties were detected and the ability of each investigated tNG to enhance skin penetration correlated well with the degree of induced stratum corneum hydration. The differences in the penetration enhancements could be attributed to the chemical structures of the nanogels used in this study. The most effective stratum corneum hydration was detected for nanogels having additional or more exposed polyether structure in their chemical composition.

Application of FT-IR Microspectroscopy in the Investigation of the Stratum Corneum Barrier Function

FT-IR microspectroscopy is acombination of FT-IR spectroscopy and optical microscopy in whichthe samples are magnified by the optical microscope, while infrared spectroscopy provides information on molecular chemistry. This combination has proven to be a highly beneficial technique with wide potential of applications principally in the biological and biomedical research areas in which samples of high complexity and intrinsic heterogeneity are investigated. Recently, IR microspectroscopy has been introduced as a powerful tool for investigation of whole skin and stratum corneum (SC) composition and heterogeneity; it also represents a method to study the effect of penetration enhancement approaches on the biochemical properties of the SC, giving important information related to the mechanism through which penetration enhancers modulate the barrier function of the SC. Visualization of the percutaneous permeation of exogenous agents is also feasible by this technique. The biochemical composition of the SC has important implications for understanding its barrier function hence, the impact of some penetration enhancers on the biochemical composition and structural alterations of the SC, mainly lipids and proteins, is illustrated in this study. Specific regions of the IR spectrum of the SC are sensitive to lipid chain conformational order and packing, and protein secondary structure thus; very useful information can be obtained concerning alteration of the structural properties of the endogenous skin components and the mechanisms of penetration enhancement. Large number of IR spectra for each investigated sample were obtained by IR mapping technique and principal component analysis, in the form of score and loadings plots, was performed to analyze the results. Changes in the structure of the SC was also observed using other techniques like differential scanning calorimetry and permeation studies.

Chemical Penetration Enhancers for Transdermal Drug Delivery - Success and Challenges.

Chemical penetration enhancers (CPEs), which are also referred to as sorption promoters or accelerants have several advantages in transdermal drug delivery. These are painlessness, noninvasiveness and the capacity to increase in transdermal flux in comparison with passive diffusion. Several investigators have used a number of chemical enhancers to demonstrate these important properties. Studies have also been carried out to have a better understanding of the mechanisms of penetration enhancement. It has been postulated that these compounds can enhance transdermal drug delivery by perturbing the stratum corneum, increasing partition coefficient or increasing solubility. In this paper, several compounds used in facilitating percutaneous penetration of drugs have been described and the potential of using them for transdermal drug delivery highlighted. Special attention has been paid to cell-penetrating proteins (protein transduction domains) as well as skin penetrating peptides. Ironically, these are substances that possess high molecular weight themselves but are capable of creating pores through which drugs can penetrate into and through the skin. Concerns relating to irritation and cytotoxicity and efforts to overcome them are discussed.

Interaction of menthol with mixed-lipid bilayer of stratum corneum: A coarse-grained simulation study

Menthol is a widely used penetration enhancer in clinical medicine due to its high efficiency and relative safety. Although there are many studies focused on the penetration-enhancing activity of menthol, the details of molecular mechanism are rarely involved in the discussion. In this study, we present a series of coarse-grained molecular dynamics simulations to investigate the interaction of menthol with a mixed-lipid bilayer model consisting of ceramides, cholesterol and free fatty acids in a 2:2:1 molar ratio. Taking both the concentration of menthol and temperature into consideration, it was found that a rise in temperature and concentration within a specific range (1–20%) could improve the penetration-enhancing property of menthol and the floppiness of the bilayer. However, at high concentrations (30% and more), menthol completely mixed with the lipids and the membrane can no longer maintain a bilayer structure. Our results elucidates some of the molecular basis for menthol’s penetration enhancing effects and may provide some assistance for the development and applications of menthol as a penetration enhancer. Furthermore, we establish a method to investigate the penetration enhancement mechanism of traditional Chinese medicine using the mixed-lipid bilayer model of stratum corneum by molecular dynamics simulations.

Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

Comparison of enhancement of transdermal permeability of Carvedilol through physical and chemical methods

Background The aim of the study was to overcome the difficulties raised in oral therapy; there is a need for the development of new drug delivery system that will improve the therapeutic efficacy. Because of its low dose and extensive hepatic metabolism, Carvedilol is a suitable candidate for transdermal administration. Objective The ultimate aim of this study was to administer Carvedilol through a transdermal patch and to evaluate by chemical method and iontophoresis by means of in-vitro drug release and ex-vivo permeation studies. Materials and methods The matrix type transdermal patches were prepared by solvent evaporation technique. Various formulations composed of hydroxypropyl methylcellulose (HPMC E15), Eudragit (ERL 100) in different ratios were prepared. All formulations consist of 15% v/w of dibutyl phthalate as plasticizer. Results and conclusion The prepared patches were characterized for various physicochemical parameters. The penetration-enhancing mechanism of iontophoresis was found to increase solvent flow through electro-osmosis and pore enlargement in the skin barrier, together with enhancement of electrochemical potential difference across the skin. The effect of chemical enhancer d-limonene and iontophoretic transdermal transport of drug using a current density of 1 mA/cm 2 was investigated. Increasing the applied current density from 0.5 to 1 mA/cm 2 resulted in a 2.2-fold increase in iontophoretic flux. Results demonstrated that iontophoresis exhibited a great ability to enhance the flux of drug in comparison with the chemical method. The optimized formulations F2 and F3 containing 8% d-limonene as chemical enhancer showed maximum skin permeation, 979.45 ± 3.16 and 900.57 ± 2.8 μg/cm 2 , respectively, whereas formulations F9 and F10 with iontophoresis showed the skin permeation, 1048.7 ± 3.8 and 1476.7.7 ± 4.8 μg/cm 2 , respectively, and obtained flux greater than F2.