Skin Penetration Rate Research Articles

Invasomes: An Artificial Vesicle Nanocarrier to Enhance Transdermal Drug Delivery

Abstract: The greatest and most noticeable organ in the body is the skin. The stratum corneum, or top layer of skin, acts as a vital barrier to prevent skin penetration for many drugs. To over-come this barrier, numerous nanocarrier frameworks have been developed, which are important for the functioning of active agents. Vascular systems known as invasomes contain low levels of ethanol as well as terpenes or terpene combinations, which have a higher skin penetration rate and function as potential carriers. Improved drug delivery via the skin using a carrier that can pene-trate these barriers presents a wide range of difficulties and possibilities for further study and the creation of new and better treatment options. The main objective of an invasome-based delivery system is to significantly improve patient compliance and therapeutic value, in addition to bol-stering the safety and efficacy of the drug. This article gives a summary of the synthesis process, invasome characterizations, penetration mechanisms, and applications. This review paper also in-cludes phospholipids and their classification. Phospholipids are present in the cell membrane and provide ceramide, a bioactive molecule that moisturizes skin and protects against environmental damage in transdermal drug delivery systems. Pharmaceutical studies demonstrate that many drug molecules have less solubility, stability, bioavailability, and penetrating power. Invasomes repre-sent a novel dosage form with promising properties for enhancing transdermal drug delivery.

Immediate dry decontamination using efficient absorbent materials is beneficial following skin exposure to low-volatile toxic chemicals.

In a chemical mass casualty incident requiring skin decontamination, dry removal using absorbent materials may be beneficial to enable immediate decontamination. The efficacy of absorbent materials has therefore been evaluated, alone or procedures including both dry and wet decontamination, following skin exposure to two low volatile toxic chemicals using an in vitro human skin penetration model. Additionally, removal using active carbon wipes was evaluated with or without the Dahlgren Decon solution. All dry decontamination procedures resulted in a significantly decreased skin penetration rate of the industrial chemical 2-butoxyethanol compared to the control without decontamination. Wet decontamination following dry absorption significantly improved the efficacy compared to dry removal alone. Dry decontamination post-exposure to the chemical warfare nerve agent VX showed no decontamination efficacy. However, dry and wet decontamination resulted in a decreased agent skin penetration rate during the last hour of the experiment. At -15°C, significantly reduced VX skin penetration rates were demonstrated for both dry decontamination alone and the dry and wet decontamination procedure. The Dahlgren Decon solution significantly reduced the amount of VX penetrating the skin, but the active carbon wipe alone did not impact the skin penetration rate. In conclusion, absorbent materials are beneficial for the removal of low-volatile chemicals from the skin, but the degree of efficacy varies between chemicals. Despite the variability, immediate dry decontamination using available absorbent materials prior to wet decontamination is recommended as a general procedure for skin decontamination. The procedure should also be prioritized in cold-weather conditions to prevent patient hypothermia.

Innovative freeze-drying technique in the fabrication of dissolving microneedle patch: Enhancing transdermal drug delivery efficiency.

Microneedle patch (MNP) has become a hot research topic in the field of transdermal drug delivery due to its ability to overcome the stratum corneum barrier. Among the various types of microneedles, dissolving microneedles represent one of the most promising transdermal delivery methods. However, the most used method for preparing dissolving microneedles, namely microfabrication, suffers from issues such as long drying time, susceptibility to humidity, and large batch-to-batch variability, which limit the development of dissolving microneedles. In this study, we report for the first time a method for preparing dissolving microneedles using freeze-drying technology. We screened substrates suitable for freeze-dried microneedle patch (FD-MNP) and used coating technology to enhance the mechanical strength of FD-MNP, allowing them to meet the requirements for skin penetration. We successfully prepared FD-MNP using hyaluronic acid as the substrate and insulin as the model drug. Scanning electron microscopy revealed that the microneedles had a porous structure. After coating, the mechanical strength of the microneedles was 0.61N/Needle, and skin penetration rate was 97%, with a penetration depth of 215μm. The tips of the FD-MNP dissolved completely within approximately 60s after skin penetration, which is much faster than conventional MNP (180s). In vitro transdermal experiments showed that the FD-MNP shortened the lag time for transdermal delivery of rhodamine 123 and insulin compared to conventional MNP, indicating a faster transdermal delivery rate. Pharmacological experiments showed that the FD-MNP lowered mouse blood glucose levels more effectively than conventional MNP, with a relative pharmacological availability of 96.59 ± 2.84%, higher than that of conventional MNP (84.34 ± 3.87%), P = 0.0095. After storage under 40℃ for two months, the insulin content within the FD-MNP remained high at 95.27 ± 4.46%, which was much higher than that of conventional MNP (58.73 ± 3.71%), P < 0.0001. In conclusion, freeze-drying technology is a highly valuable method for preparing dissolving microneedles with potential applications in transdermal drug delivery.

A novel organogel of breviscapine via supramolecular self-assembly in DCM

Supramolecular gels provide great advantages for technological applications. More recently, the natural product gelators (NPGs) has been revealed as an interesting strategy to produce soft materials while combining stimuli-responsiveness and biological activities. However, the discovered NPGs till now was quite rare in spite of the enormous quantity of natural products. Herein, a supramolecular organogel with novel architecture was reported for the first time. Breviscapine (Bre), a natural flavonoid glycoside, was found to be spontaneously forming gels in dichloromethane during the ultrasonication-aided anti-solvent precipitation process. The corresponding xerogel were revealed a spherical network of packed microspheres and maintained a certain crystalline state. Hydrogen bonding and π-π stacking were confirmed as the main driving forces for the self-assembly of the organogel by FTIR, NMR and molecular dynamic simulation analysis. Moreover, the obtained Bre organogel showed excellent solvent-retention property and higher skin penetration rate than the pure drug. These would be of great benefit for future discovery of new NPGs and exploration on novel applications of NPG-based gels.

Biodegradable and dissolvable resveratrol nanocrystals non-silicon microneedles for transdermal drug delivery

The prevalence and lethality of cutaneous melanoma have increased in recent years. Lower skin penetration rates and poor soluble affect the effective delivery of resveratrol. To overcome these two issues, a biodegradable and dissolvable resveratrol nanocrystals non-silicon microneedles was designed in this study. The nanocrystals technology was used to improve the resveratrol solubility. Transmission electron microscopy and scanning electron microscopy demonstrated that the amorphous resveratrol nanocrystals were successfully prepared with a particle size of 161 ± 9 nm and presented a superior performance in vitro dissolution of 84.14 ± 2.53% for 120 min. For the skin permeability issue, a dissolvable microneedle, made with a biocompatible and biodegradable polymer (a mixture of polyvinylpyrrolidone and polyvinyl alcohol), exhibited exceptional mechanical strength even the microneedles matrix was loaded with the drug for 1.26 N/needle. The z-axis scanning also exhibited the uniformity of rhodamine B within the needle. And it presented rapid resveratrol releases after puncture into the mice's skin. The dissolvable microneedles loaded with the resveratrol nanocrystals provided an efficient and convenient transdermal delivery system.

Functionalized multiwalled carbon nanotube-ethosomes for transdermal delivery of ketoprofen: Ex vivo and in vivo evaluation

Transdermal administration is a promising non-invasive and convenient method of drug delivery in clinic and avoid serious gastrointestinal adverse reactions. In this study, a hybrid nanocarrier was developed to facilitate transdermal delivery of drugs. The low water-soluble ketoprofen (KP) was ultrasonically loaded on functionalized multi-walled carbon nanotubes (f-MWCNTs), and the preparation process was optimized using Box-Behnken design. Then, KP-loaded f-MWCNTs composite ethosomes (f-MWCNTs-KP-ES) were prepared by a single-step injection technology. Over the study period, the preparation was verified by a series of characterizations, and ex vivo release characteristics, ex vivo permeation of rat skin and in vivo pharmacokinetics were studied. The characterization results consistently showed that f-MWCNTs-KP-ES were successfully prepared. The preparation can obviously improve the solubility of KP. Ex vivo permeation experiments showed that had a sustained release effect and the skin penetration rate of f-MWCNTs-KP-ES gel is the fastest, with a cumulative permeation amount of 602.35 ± 41.06 μg/cm2. In addition, both ethosomes and f-MWCNTs could increase the retention of drugs and form drug reservoirs. Fluorescence microscope images of rat skin clearly illustrated the faster and deeper penetration of f-MWCNTs composite ethosomes formulation loaded with rhodamine B (RB) (f-MWCNT-RB-ES). In vivo pharmacokinetic experiments showed the area under the drug time curve (AUC0-t) and elimination half-life (T1/2β) of f-MWCNTs-KP-ES gel group were significantly increased and prolonged compared with KP commercial gel group, respectively. The overall data indicate that the f-MWCNTs composite ethosomes formulation is a promising transdermal drug delivery system.

Iontophoresis-driven porous microneedle array patch for active transdermal drug delivery

A transdermal patch that combines microneedle array (MA) with iontophoresis can achieve synergistic and remarkable enhancement of drug delivery with precise electronic control. However, the development of an MA patch combined with iontophoresis that can enable in situ treatment, easy self-administration, and controllable delivery of liquid macromolecular drugs is still a challenge. Here, we presented an iontophoresis-driven porous MA patch (IDPMAP) for in situ, patient-friendly, and active delivery of charged macromolecular drugs. IDPMAP integrates porous MA with iontophoresis into a single transdermal patch, thus realizing the one-step drug administration strategy of “Penetration, Diffusion, and Iontophoresis.” Moreover, a matching portable iontophoresis-driven device was developed for drug self-administration of IDPMAP. In vitro and in vivo studies showed that IDPMAP had approximately 99% skin penetration rate, negligible cytotoxicity, and good biocompatibility without skin irritation and hypersensitivity. In vivo transdermal delivery of insulin in type 1 diabetic rats demonstrated that IDPMAP could effectively deliver insulin nanovesicles and produce a robust hypoglycemic effect on the rats (maintain normal blood glucose for approximately 5.4 h), with more advanced controllability and efficiency than that achieved by pristine MA or iontophoresis. IDPMAP and its portable iontophoresis-driven device are user-friendly and thus show a promising potential for drug self-administration at home.

Effect of Alkyl Structure (Straight Chain/Branched Chain/Unsaturation) of C18 Fatty Acid Sodium Soap on Skin Barrier Function

Anionic surfactants are commonly used as detergents and emulsifiers. However, these compounds are potent skin irritants. In this study, we evaluated the effect of the alkyl structure of anionic surfactants on the skin barrier function using the transmission index (TI) method. The TI method is used to measure the skin penetration rate of drugs. Sodium soaps of C18 fatty acids with different structures were evaluated. Sodium laurate was used as the control. In addition, microscopic observations of the skin tissue treated with different soaps and controls were performed to study the mechanism of skin permeation. Results showed that unsaturated fatty acid soaps exerted the most potent effect on the skin barrier function and saturated fatty acid soaps exerted the least effect; saturated branched fatty acid soap had an intermediate effect. This could be attributed to the differences in the melting points of different fatty acids. In addition, unlike lauric acid soap, C18 fatty acid soap did not cause morphological changes in the skin tissue. Thus, differences in the alkyl structure of fatty acids resulted in differences in the effect of fatty acid soaps on the skin barrier function. The mechanism was presumed to be an effect on intercellular lipids.

Development and Characterization of Niosomal Gel System using Lallementia royaleana Benth. mucilage for the treatment of Rheumatoid Arthritis.

Niosomes structural framework comprises of non-ionic surfactant-based microscopic lamellar structures which carries the potential to sustain the effect of drug from its delivery system. In present work, the attempt was made to identify the effect of different ingredients such as effect of Tweens and natural mucilage of Lallemantia royaleana Benth. on the performance of developed niosomal gel formulations in order to prolong the duration of action of drug and to minimize its side effects of topical conventional drug administration. All Ibuprofen loaded niosomes formulationswere prepared by ether injection method; using cetosteryl alcohol with different variants of Tweens and Spans. Various evaluation parameters were performed to confirm niosome formation. Further, the niosomes were incorporated into gel system and evaluated for in-vitro permeability study (ex-vivo) on excised rat skin by membrane diffusion method and in-vivo study by carrageenan induced rat paw edema model. The best selected niosome formulation F9 gave no sedimentation, layer separation and unchanged particle shapes and thus selected for gel preparation using Lallemantia royaleana Benth. mucilage and carbopol in different ratios. Ex-vivo and in-vivo studies indicated high skin retention and penetration rates within the skin for tests niosomal gel formulations (G1 & G2). The present study suggested that developed topical gel formulation provides enhance permeability and longer duration of drug action over conventional gels.

Systematic Evaluation of Lipophilicity in Correlation with Pharmacophore Identification to Develop Potent Bacterial Inhibitors

The widespread drug resistances against bacteria have been increased at an alarming rate and coerce to develop new designs with improved potency. Pharmacophore is the part of a molecular structure that responsible for a particular biological or pharmacological interaction. Lipophilicity is one of the key factors that play a crucial role in designing novel antibacterial agents. This parameter has been used in connection with blood–brain barrier (BBB) distribution or intestinal drug absorption and is sculpting by partition of a solute between n-octanol and water (LogP). It has been shown that increased lipophilicity can be correlated with increased biological activity, poorer aqueous solubility, more rapid metabolism and elimination, increased rate of skin penetration, increased plasma protein binding and faster action. Therefore, the purpose of this study is to estimate Lipophilicity in correlation with pharmacophoric nature of the compounds. In this study, a series of pyrazole derivatives were prepared through Schiff base condensation. Different groups were tuned as toxicophore at one end of molecular framework in order to identify their pharmacophoric function. All molecules were characterized through spectroscopic methods viz. IR, ESI–MS, 1H-NMR, 13C-NMR and elemental analysis. Antibacterial activities of all the derivatives were evaluated against Escherichia coli and Mycobacterium tuberculosis in comparison to standard drugs. The compound 4-bromo-N-((5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)methylene)benzenamine (2j) was found the most promising among others with cytotoxicity 33.5 µg/mL determine through Brine Shrimp lethality bioassay. Electron withdrawing groups play a significant role in lipophilic control and inhibition action.

Role of Polyvinylpyrrolidone in Dissolving Microneedle for Efficient Transdermal Drug Delivery: In vitro and Clinical Studies

The purpose of this study is to find an optimum composition of microneedles that penetrate the skin and rapidly dissolve within the cutaneous layer in a few minutes. A micromolding method was introduced to prepare drug‐loaded dissolving microneedles by using biocompatible, water‐soluble polymers such as carboxymethylcellulose, hyaluronic acid, and polyvinylpyrrolidone (PVP). The microneedles had a sharp structure with a needle tip of about 5 μm. The microneedles penetrated into the skin with 90% skin penetration rate, and they were dissolved within minutes to release the drug. An increase in the content of PVP in the microneedle increased the dissolution rate of the microneedles in the skin and the needle strength to penetrate the skin, and resulted in an increased skin permeation of the drug. The drug‐loaded microneedles were applied to the wrinkles shown around the eyes (crow's feet) of female subjects for 8 weeks, and we observed statistically significant disappearance of wrinkle after 4 weeks. The newly developed dissolving needles showed efficient drug delivery and can be considered a valuable, high‐functioning, potential wrinkle improving treatment.

Predicting the Rate of Skin Penetration Using an Aggregated Conformal Prediction Framework.

Skin serves as a drug administration route, and skin permeability of chemicals is of significant interest in the pharmaceutical and cosmetic industries. An aggregated conformal prediction (ACP) framework was used to build models for predicting the permeation rate (log Kp) of chemical compounds through human skin. The conformal prediction method gives as an output the prediction range at a given level of confidence for each compound, which enables the user to make a more informed decision when, for example, suggesting the next compound to prepare. Predictive models were built using both the random forest and the support vector machine methods and were based on experimentally derived permeability data on 211 diverse compounds. The derived models were of similar predictive quality as compared to earlier published models but have the extra advantage of not only presenting a single predicted value for each compound but also a reliable, individually assigned prediction range. The models use calculated descriptors and can quickly predict the skin permeation rate of new compounds.

The Effect of Particle Size on the Deposition of Solid Lipid Nanoparticles in Different Skin Layers: A Histological Study.

In the present study the effect of particle size, as a substantial parameters in skin penetration, on the deposition depth and rate of SLNs in different layers of skin was explored. SLNs in different particle size ranges (80, 333 and 971 nm) made of Precirol as solid lipid were prepared using hot melt homogenization technique and pigmented by Rhodamine B to be able to be tracked in the skin under inspection of fluorescent microscopy. After 0.5 h, 3 h, 6 h and 24 h of SLNs administration on rat skin, animals were sacrificed and exercised skins were sliced by a freeze microtome. SLNs were monitored in the skin structure under fluorescence microscope. The size of SLNs played a crucial role in the penetration to deep skin layers. The sub100 nm size range of SLNs showed the most promising skin penetration rate and depth mainly via hair follicles. The results of the present study indicated that the selection of an appropriate size of particles may be a valuable factor impacting the therapeutic outcomes of dermal drug administration.

The Effect of Particle Size on the Deposition of Solid Lipid Nanoparticles in Different Skin Layers: A Histological Study.

In the present study the effect of particle size, as a substantial parameters in skin penetration, on the deposition depth and rate of SLNs in different layers of skin was explored. SLNs in different particle size ranges (80, 333 and 971 nm) made of Precirol as solid lipid were prepared using hot melt homogenization technique and pigmented by Rhodamine B to be able to be tracked in the skin under inspection of fluorescent microscopy. After 0.5 h, 3 h, 6 h and 24 h of SLNs administration on rat skin, animals were sacrificed and exercised skins were sliced by a freeze microtome. SLNs were monitored in the skin structure under fluorescence microscope. The size of SLNs played a crucial role in the penetration to deep skin layers. The sub100 nm size range of SLNs showed the most promising skin penetration rate and depth mainly via hair follicles. The results of the present study indicated that the selection of an appropriate size of particles may be a valuable factor impacting the therapeutic outcomes of dermal drug administration.

Preparation of Solid Lipid Nanoparticle Containing Tocopheryl Acetate and Its Encapsulation Efficiency

Various forms of cosmetics have been studied in order to increase the skin penetration rate of active ingredients. Solid lipid nanoparticles (SLNs) that can continuously release an active ingredient for many days by encapsulating a drug in polymer nanoparticles were prepared and analyzed to determine encapsulation efficiency by: 1) the type and quantity of surfactant, 2) agitation speed, and 3) dispersion temperature. To prepare SLNs encapsulating tocopheryl acetate, the concentration of stearic acid was fixed to 1 wt%, the concentrations of surfactants (Tween 20 and Tween 80) studied were 1, 4, and 10 wt%, the agitation speeds tested were 1,000 rpm and 2,000 rpm, and the dispersion temperatures used were 4℃ and 25℃. The 1 wt% Tween 20, along with 1 wt% and 4 wt% Tween 80 SLNs showed standardized granular shapes, and 1 wt% Tween 80 SLN at 4℃ and 2,000 rpm showed the smallest particle size of 303 nm. The zeta potential in all SLNs produced ranged from -20.4 mV to -39.3 mV, showing a high degree of stability, while 4 wt% Tween 80 SLN at 4℃ and 2,000 rpm showed the highest encapsulation efficiency of 80.8%. Therefore, it is confirmed that both the type of surfactant used and the dispersion temperature, along with the mix ratio of lipid and surfactant are important factors for the production of SLNs with high skin absorption rates.

Penetration of titanium dioxide nanoparticles through slightly damaged skin in vitro and in vivo.

Titanium dioxide nanoparticles (TiO2-NPs) have been widely developed for versatile use, but the potential risk form their skin exposure is still unclear. To evaluate this risk, the skin penetration of TiO2-NPs is necessary to be understood first. The aims of this study are to investigated the penetration of TiO2-NPs through slightly damaged skin and intact skin in vitro and in vivo. TiO2-NPs with a diameter of 20 nm was labeled with 125I.The skin of rat was treated with 2% SLS solution and obtained as slightly damaged skin. The 125I labeled TiO2-NPs (125I-TiO2-NPs)solution and 0.9% PS solution were added into the donor chamber and receptor chamber of static diffusion cells which clamped the skin at the middle of two half-cells, respectively. During 24 hours, samples were extracted from the receptor chamber and counted for 1 min using γ-counter to detect the radioactivity. The skin penetration of TiO2-NPs in vitro was expressed as the percentage of radioactivity of receptor chamber solution compared with total radioactivity in the donor chamber. Thereafter, the 125I-TiO2-NPs was exposed to the rats. After 1 day and 3 days, the blood and tissues of rats were harvested, weighed and counted for 1 min using γ-counter to detect the tissue radioactivity. The skin penetration of TiO2-NPs in vivo was expressed as the percentage dose per gram tissue (% dose/g). In the skin penetration experiment in vitro, the radioactivity of receptor chamber solution through damaged skin was higher than that of through intact skin and was about 2% radioactivity of donor chamber on 24 h. In the skin penetration experiment in vivo, the radioactivity of blood and tissues of rats after exposing to 125I-TiO2-NPs solution though damaged skin or intact skin were less than 0.05% dose/g on 1 d and quickly declined on 3 d. The skin penetration rates of TiO2-NPs through slightly damaged skin and intact skin in vitro and vivo were lower than the rate of free 125I in the TiO2-NPs solution. The TiO2-NPs could not penetrate through the damaged skin or intact skin both in vitro and in vivo. It suggested that the TiO2-NPs should be safe when it was applied and contacted with skin.

The Relationship between Solubility and Transdermal Absorption of Tadalafil.

The aim of this study was to find a relationship between drug solubility and its transdermal permeation and find the best vehicle composition to improve transdermal permeation of Tadalafil. Pure or binary mixtures of commonly used solvents in pharmaceutical sciences including ethanol, glycerin, N-methyl pyrrolidone (NMP), polyethylene glycol (PEG) 400 and propylene glycol (PG) were evaluated for drug solubility and transdermal delivery through the exercised rat skin employing Franz diffusion cells. Tadalafil showed higher solubility in NMP compared to the other solvents. The amount of Tadalafil permeation from the pure vehicles was ranked as follow: Ethanol >glycerin >NMP>PEG 400 >PG. Furthermore, the solubility and transdermal delivery from binary mixtures of NMP and PG were higher than that obtained from pure PG, and accordingly, both increased with increasing NMP concentration in the binary solvent mixtures. The Flux values were determined as following order for Ethanol>NMP>glycerin>PG>PEG 400. Generally, increase in Tadalafil solubility resulted in a decrease in its skin penetration rate and amount. However, NMP exhibited substantial drug skin penetration rate and amount accompanying with appropriate drug solvency. In conclusion, the results of this study introduced NMP as a solvent suitable for application in the formulation of topically applied drug delivery systems.

Extrapolation of systemic bioavailability assessing skin absorption and epidermal and hepatic metabolism of aromatic amine hair dyes in vitro

Approaches to assess the role of absorption, metabolism and excretion of cosmetic ingredients that are based on the integration of different in vitro data are important for their safety assessment, specifically as it offers an opportunity to refine that safety assessment. In order to estimate systemic exposure (AUC) to aromatic amine hair dyes following typical product application conditions, skin penetration and epidermal and systemic metabolic conversion of the parent compound was assessed in human skin explants and human keratinocyte (HaCaT) and hepatocyte cultures. To estimate the amount of the aromatic amine that can reach the general circulation unchanged after passage through the skin the following toxicokinetically relevant parameters were applied: a) Michaelis–Menten kinetics to quantify the epidermal metabolism; b) the estimated keratinocyte cell abundance in the viable epidermis; c) the skin penetration rate; d) the calculated Mean Residence Time in the viable epidermis; e) the viable epidermis thickness and f) the skin permeability coefficient. In a next step, in vitro hepatocyte Km and Vmax values and whole liver mass and cell abundance were used to calculate the scaled intrinsic clearance, which was combined with liver blood flow and fraction of compound unbound in the blood to give hepatic clearance. The systemic exposure in the general circulation (AUC) was extrapolated using internal dose and hepatic clearance, and Cmax was extrapolated (conservative overestimation) using internal dose and volume of distribution, indicating that appropriate toxicokinetic information can be generated based solely on in vitro data. For the hair dye, p-phenylenediamine, these data were found to be in the same order of magnitude as those published for human volunteers.

DIS에 의한 Polyethylene Glycol 함침 알로에 베라 겔의 보습 및 경피흡수 특성

This study was carried out to investigate the in vitro and in vivo moisturizing properties and percutaneous absorption of PEG-impregnated Aloe vera gel. The PEG-i-Aloe gel was obtained from dewatering and impregnation by soaking (DIS) of Aloe vera leaf slice. The moisturizing property of the obtained sample was evaluated by moisture determination using gravimetric method in desiccator under different RH% and by water sorption-desorption test on human skin. The transdermal penetration characteristics of PEG-i-Aloe gel was investigated by Franz diffusion cell in vitro transdermal absorption method. PEG-i-Aloe gel had high moisture retention ability and could significantly lead the enhancing skin hydration status as well as reducing the skin water loss due to the film formation as a skin barrier. The skin penetration rate of PEGi- Aloe gel at steady state was 9.76 <TEX>${\mu}g/(h{\cdot}cm^2)$</TEX> and the quantity of the transdermal absorption was 144 <TEX>${\mu}g/cm^2$</TEX> in 9 hr. The penetration mechanism was well fitted with Higuchi model (<TEX>$R^2$</TEX> = 0.974-0.994). The results show that PEG-i-Aloe gel has the significant moisturizing effect and strong penetration of the animal skin. It could be used as the moisturizing additive in cosmetic skin products.

Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure

The absorption and excretion of the insect repellent IR3535® was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535®, i.e. the amounts of IR3535® applied were between 1.94 and 3.4mmol/person (418–731mg/person). Blood and urinary concentrations of IR3535® and its only metabolite, IR3535®-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535® were at or below the limit of quantification (0.037μmol/L). IR3535®-free acid peaked in plasma samples 2–6h after dermal application. Cmax mean values were 5.7μmol/L in males, 3.0μmol/L in females and 4.2μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9μmolL−1h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535® and IR3535®-free acid were detectable, however, only very small amounts of IR3535® were found. Concentrations of IR3535®-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535® and IR3535®-free acid excreted with urine over 48h representing 13.3±3.05% of the dose applied. Since IR3535® is rapidly and extensively metabolized, and IR3535®-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535®-free acid and IR3535® represents the total extent of absorption of IR3535® in humans. Based on the results of this study, the skin penetration rate of IR3535® is 13.3% in humans after dermal application.