Influence of mechanical skin treatment (massage, ultrasound, microdermabrasion, tape stripping and microneedling) on dermal penetration efficacy of chemical compounds.

The influence of mechanical skin treatments (massage, ultrasound, microdermabrasion, tape stripping and microneedling) on the dermal penetration efficacy was investigated. Results show that microneedling was the most effective tool. It increased the penetration efficacy (amount of penetrated active and penetration depth) by a factor > 2. Microdermabrasion and tape stripping remove parts of the stratum corneum (SC). This reduces the barrier function and increases the penetration efficacy. Microdermabrasion removed about 23% of the SC. Tape stripping removed about 34% of the SC and thus resulted in a slightly more pronounced increase in the penetration efficacy (+31% after tape stripping and +18% after microdermabrasion). Massage and skin treatment with ultrasound decreased the penetration efficacy by about one third when compared to skin where the formulations were applied without any mechanical treatment. The penetration reducing effect is caused by mechanical stress (pressure), which reduces the thickness of the SC. The increased density of the SC is considered to decrease the intercellular space within the SC and with this the flux for chemical compounds. Therefore, massage and other mechanical treatments that increase the density of the SC should be avoided if efficient dermal penetration is required.

Permeation, stability and acute dermal irritation of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica crude extract loaded transdermal gels.

In this study, permeation behaviors and chemical stability of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica (PM), Thai traditional medicine, crude extract containing transdermal gels were firstly evaluated. Three different PM extract containing gels were formulated, including hydroalcoholic and microemulsion gels using carbomer, and silicone gel using silicone elastomer. In vitro permeation through porcine ear skin demonstrated that the flux and 24 h cumulative permeation of miroestrol and deoxymiroestrol were in the order of hydroalcoholic > silicone > microemulsion gels. Hydroalcoholic gel provided the highest partition coefficient from gel onto skin, and thus the skin permeability coefficient. After 24 h permeation, no miroestrol and deoxymiroestrol remained deposited in the skin. Accelerated study using heating-cooling revealed insignificant difference between the remaining percentages of miroestrol and deoxymiroestrol in aqueous and non-aqueous based gels. Long-term stability study showed that miroestrol contents remained constant for 90 d and 30 d under 5 ± 3 °C and 30 ± 2 °C, 75 ± 5%RH, respectively; whereas the percentage of deoxymiroestrol decreased significantly after 30 d storage, irrespective of storage conditions. Acute dermal irritation test on New Zealand White rabbits showed that PM hydroalcoholic gels were non-irritant, with no signs of erythema or oedema.[Figure: see text].

Profiling skin penetration using PEGylated emulsifiers as penetration enhancers via confocal Raman spectroscopy and fluorescence spectroscopy.

Non-ionic emulsifiers have been continuous research focus in skin analysis. With the aim of finding their role as penetration enhancers in dermal drug delivery systems, PEGylated emulsifiers of polyethylene glycol (PEG) ethers were targeted to be investigated ex-vivo. The effectiveness of them in the enhancement of skin penetration was examined by conventional tape stripping method and confocal Raman spectroscopy (CRS). Fluorescein sodium salt (Fluo-Na) and procaine HCl were respectively used as model drugs. The drug delivery performances were compared in the aspects of penetration amount and depth. Based on the results from both analyses, all investigated emulsifiers have the ability to enhance the amount of drug penetration. PEG-20 ethers showed higher ability than PEG-2 oleyl ether (O2) in promoting drug distribution by depth, especially PEG-20 cetyl ether (C20) showed a distinct effect. According to this study, their penetration enhancing performances seem to be linked to their interruption of intercellular lipids, which can be considered as the underlying mechanism for governing the ability of PEGylated emulsifiers as penetration enhancers. Further instrumental comparison highlighted the benefits of using CRS as an alternative in skin penetration analysis.

Development of omega-3 loxoprofen-loaded nanoemulsion to limit the side effect associated with NSAIDs in treatment of tooth pain.

The majority of newly developed drugs need to be incorporated with delivery systems to maximize their effect and minimize side effects. Nanoemulsions (NEs) are one type of delivery system that helps to improve the solubility and dissolution of drugs, attempting to enhance their bioavailability and onset of action. The objective of this investigation was to develop an omega-3 oil-based NE loaded with loxoprofen (LXP) to enhance its dissolution, in vitro release, and mucosal penetration and decrease its mucosal ulcerative effects when applied in an oral treatment. LXP-loaded NEs were formulated with varying levels of omega-3 oil (10-30%), surfactant polyoxyethylene-C21-ethers (laureth-21) (40-60%), and co-surfactant polyethylene glycol-40 hydrogenated castor oil (HCO-40) (30-50%) using an extreme vertices mixture design. The developed NEs were characterized for globule size and drug loading capacity. The optimal formulation was tested for in vitro drug release, ex vivo permeation, and ulcer index value. The developed NE acquired a globule size ranging 71-195 nm and drug loading capacity of 43-87%. Considering the results of the in vitro release study, the optimized NE formulation achieved 2.45-fold and 2-fold increases in drug permeation across tested mucosa compared to a marketed tablet and drug aqueous dispersion, respectively. Moreover, the optimum NE exhibited the best ulcer index in comparison to drug aqueous suspension and different formulations when tested in rats. Overall, this research highlights the capacity of NEs to deliver LXP with enhanced solubility, drug release, and permeation while effectively protecting the application site from side effects of the model drug.

Statistical Considerations in Assessing In Vivo Adhesion with Transdermal and Topical Delivery Systems for New Drug Applications.

Proper adhesion plays a critical role in maintaining a consistent, efficacious, and safe drug delivery profile for transdermal and topical delivery systems (TDS). As such, in vivo skin adhesion studies are recommended by regulatory agencies to support the approval of TDS in new drug applications (NDAs). A draft guidance for industry by the US Food and Drug Administration outlines a non-inferiority comparison between a test product and its reference product for generic TDS in abbreviated new drug applications (ANDAs). However, the statistical method is not applicable for evaluating adhesion of TDS for NDAs, because no reference product exists. In this article, we explore an alternative primary endpoint and a one-sided binomial test to evaluate in vivo adhesion of TDS in NDAs. Statistical considerations related to the proposed approach are discussed. To understand its potential use, the proposed approach is applied to data sets of in vivo adhesion studies from selected NDAs and ANDAs.

Glutathione Counteracts the Effects of Japanese Cedar (Cryptomeria japonica) Pollen Allergen Cry j1.

Japanese cedar (Cryptomeria japonica) pollen allergen Cry j1 increases the intracellular calcium concentration in human keratinocytes, and also impairs the epidermal barrier function. Here, we show that reduced glutathione (GSH) blocks both thrombin activation and the Cry j1-induced intracellular calcium elevation in cultured human keratinocytes, and also prevents the Cry j1-induced decrease of barrier function in ex vivo human skin.

Dexmedetomidine and levobupivacaine co-loaded, transcriptional transactivator peptide modified nanostructured lipid carriers or lipid-polymer hybrid nanoparticles, which performed better for local anesthetic therapy?

Local anesthetics (LAs) have been widely applied in clinic for regional anesthesia, postoperative analgesia, and management of acute and chronic pain. Nanostructured lipid carriers (NLCs) and lipid-polymer hybrid nanoparticles (LPNs) are reported as good choices for LA therapy. Transactivated transcriptional activator (TAT) was reported as a modifier for the topical delivery of drugs. In the present study, TAT modified, levobupivacaine (LEV) and dexmedetomidine (DEX) co-delivered NLCs (TAT-LEV&DEX-NLCs, T-L&D-N) and LPNs (TAT-LEV&DEX-LPNs, T-L&D-L) were designed and compared for the LA therapy. T-L&D-L exhibited better efficiency in improving the skin permeation, analgesic time, and pain control intensity than T-L&D-N both in vitro and in vivo. On the other side, T-L&D-N also improved the therapeutic effect of drugs to a large extent. These two systems both exhibited superiority in some respects. TAT modified LPNs are more promising platform for the long-term local anesthesia.

Unconventional Passive Enhancement of Transdermal Drug Delivery: toward a Mechanistic Understanding of Penetration Enhancers Releasing from Acrylic Pressure-Sensitive Adhesive of Patches.

PURPOSE: Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-sensitive adhesive of patches and propose an unconventional enhancement of PEs efficacy. METHODS: PEs efficacy was evaluated both in drug permeation study and drug pharmacokinetic study. Confocal Raman spectroscopy was employed to observe PEs release behavior by mapping PEs dynamic distribution in skin. The mechanism of PEs release behavior was provided from molecular interaction and rheology using FT-IR, molecular docking, molecular dynamic simulation and rheometer, separately. RESULTS: The release behavior of PEs themselves greatly restricted their efficacy. By using PEG 400, an improvement of oleic acid (OA) release behavior was achieved, and the efficacy of OA was significantly enhanced with enhancing ratio (ER) from 2.69 to 4.10 and AUClast from 1574 ± 87 to 2664 ± 249 ng·h/mL, separately. The improvement of OA release behavior was primarily resulted from reduction of the interaction between OA and adhesive, which was caused by other small molecules with a strong ability in forming hydrogen bonds with adhesive. Also, the rigidity of adhesive was a factor in affecting PEs release behavior. CONCLUSIONS: An unconventional passive enhancement of transdermal drug delivery was achieved via improving PEs themselves releasing from acrylic pressure-sensitive adhesive. Graphical abstract Influence of PEs release behavior on drug permeation through skin and molecular mechanism.

Evaluation of Heat Effects on Transdermal Nicotine Delivery In Vitro and In Silico Using Heat-Enhanced Transport Model Analysis.

A combined experimental and computational model approach was developed to assess heat effects on drug delivery from transdermal delivery systems (TDSs) in vitro and nicotine was the model drug. A Franz diffusion cell system was modified to allow close control of skin temperature when heat was applied from an infrared lamp in vitro. The effects of different heat application regimens on nicotine fluxes from two commercial TDSs across human cadaver skin were determined. Results were interpreted in terms of transport parameters estimated using a computational heat and mass transport model. Steady-state skin surface temperature was obtained rapidly after heat application. Increasing skin surface temperature from 32 to 42°C resulted in an approximately 2-fold increase in average nicotine flux for both TDSs, with maximum flux observed during early heat application. ANOVA statistical analyses of the in vitro permeation data identified TDS differences, further evidenced by the need for a two-layer model to describe one of the TDSs. Activation energies associated with these data suggest similar temperature effects on nicotine transport across the skin despite TDS design differences. Model simulations based on data obtained from continuous heat application were able to predict system response to intermittent heat application, as shown by the agreement between the simulation results and experimental data of nicotine fluxes under four different heat application regimens. The combination of in vitro permeation testing and a computational model provided a parameter-based heat and mass transport approach to evaluate heat effects on nicotine TDS delivery.

Percutaneous absorption of resveratrol and its oligomers to relieve psoriasiform lesions: In silico, in vitro and in vivo evaluations.

Resveratrol was shown to exert anti-inflammatory effects in experimental models of psoriasis. Several natural oligomers of resveratrol have been extracted from plants. We investigated the antipsoriatic activity of topical administration of resveratrol oligomers and explored the effect of the number of resveratrol subunits on skin absorption to establish the structure-permeation relationship (SPR). Three oligomers, ε-viniferin (dimer), ampelopsin C (trimer) and vitisin A (tetramer), extracted from Vitis thunbergii root were compared to the resveratrol glycoside polydatin. Delivery to porcine skin was assessed in vitro using the Franz cell. Keratinocytes activated with imiquimod (IMQ) were utilized to evaluate cytokine/chemokine inhibition. Topical application of resveratrol and oligomers was characterized in vivo by assessing cutaneous absorption, skin physiology, proinflammatory mediator expression, and histopathology in IMQ-treated mice. Skin deposition decreased as the molecular size and lipophilicity of the permeants increased. Resveratrol exhibited highest absorption, followed by ε-viniferin. The monomers resveratrol and polydatin exhibited higher flux across skin than the larger oligomers. In silico modeling revealed the permeants that strongly interacted with stratum corneum (SC) lipids exhibited lower transport to viable skin and the receptor compartment. In vitro, resveratrol and its derivatives had comparable ability to inhibit IMQ-induced IL-1ß, IL-6, and CXCL8 secretion in activated keratinocytes. In vivo, topically applied ε-viniferin accumulated at higher levels than resveratrol (0.067 versus 0.029 nmol/mg) in psoriasis-like mouse skin with impaired barrier capacity. Topical ε-viniferin alleviated psoriasiform symptoms and reduced IL-23 secretion (by 58% vs. 37%) more effectively than resveratrol. ε-Viniferin has potential as an anti-inflammatory agent to prevent or treat psoriasis.

What is the fate of multi-lamellar liposomes of controlled size, charge and elasticity in artificial and animal skin?

Multi-lamellar liposomes (MLLs), prepared by shearing a lamellar phase composed of lipids (phosphatidylcholine) and surfactant (Tween 80®), were designed to control their size, charge and elasticity, the key parameters known to influence liposomes penetration through skin. Their size was tuned by the water content of the sheared lamellar phase, and by the surfactant-to-lipid ratio as was their elasticity. Their charge was varied by the incorporation of DPPG and DOTAP to confer a high negative or positive zeta potential, respectively. Couples of MLLs differing solely in one physicochemical parameter, the others kept constant, were compared to discriminate the influence of the key parameters on their penetration through a synthetic membrane, Strat-M™. Using confocal Raman microscopy, the kinetics of MLLs penetration was established for 40 h using a Franz cell dispositive under non-occlusive conditions. From these comparisons, we showed that their transversal diffusion cannot be predicted by one sole parameter but depends on a combination of their physicochemical characteristics that were enlightened. Two types of liposomes designed for topic and systemic diffusion and tested on dog-excised skin exhibited the predicted behavior. Eventually, a mechanism supported by complementary TEM analysis is proposed to shed light on MLLs skin penetration.

In vitro and in vivo studies of micro-depots using tailored microemulsion for sustained local anaesthesia.

In clinical practice, lidocaine is used as local anesthetic for the management of post-operative pain. The commercial formulation including gels, injections and ointments showed short duration of action (1 to 2 h). In this paper, the efforts have being made to develop tailored lidocaine-microemulsion (o/w), which on penetration in the skin layer cause micro-depots formation due to destabilization of the microemulsion system. To identify the microemulsion region, pseudo ternary diagrams were constructed using Capmul MCM as oil, Pluronic F68 as tri-block surfactant, polyethylene glycol 200 as co-surfactant at 1:4 and 1:6 ratios (S:Co-S). The selected 5%w/v lidocaine loaded microemulsion [Ld-ME-2(1:4)] was stable in thermodynamic test and during shelf life period (3 months). In ex vivo permeability study, the lidocaine release from Ld-ME-2(1:4) microemulsion was sustained in comparison to the marketed lidocaine ointment. The skin irritation study confirmed the safety of lidocaine loaded microemulsion. Tail flick test showed improved and sustain local anaesthetic effect in comparison to the market ointment. The improved efficacy of microemulsion system, was due to high penetration in the skin layer due to local precipitation of lidocaine from microemulsion. The findings suggest that the tailored microemulsion could be a potential strategy to prolong the local anaesthesia.

Effects of lecithin-based nanoemulsions on skin: Short-time cytotoxicity MTT and BrdU studies, skin penetration of surfactants and additives and the delivery of curcumin.

Surfactants are important ingredients in pharmaceutical and cosmetic formulations, as in creams, shampoos or shower gels. As conventional emulsifiers such as sodium dodecyl sulfate (SDS) have fallen into disrepute due to their skin irritation potential, the naturally occurring lecithins are being investigated as a potential alternative. Thus, lecithin-based nanoemulsions with and without the drug curcumin, known for its wound healing properties, were produced and characterised in terms of their particle size, polydispersity index (PDI) and zeta potential and compared to SDS-based formulations. In vitro toxicity of the produced blank nanoemulsions was assessed with primary human keratinocytes and fibroblasts using two different cell viability assays (BrdU and EZ4U). Further, we investigated the penetration profiles of the deployed surfactants and oil components using combined ATR-FTIR/tape stripping experiments and confirmed the ability of the lecithin-based nanoemulsions to deliver curcumin into the stratum corneum in tape stripping-UV/Vis experiments. All manufactured nanoemulsions showed droplet sizes under 250 nm with satisfying PDI and zeta potential values. Viability assays with human skin cells clearly indicated that lecithin-based nanoemulsions were superior to SDS-based formulations. ATR-FTIR tests showed that lecithin and oil components remained in the superficial layers of the stratum corneum, suggesting a low risk for skin irritation. Ex vivo tape stripping experiments revealed that the kind of oil used in the nanoemulsion seemed to influence the depth of curcumin penetration into the stratum corneum.

Topical application of nanoparticles integrated supramolecular hydrogels for the potential treatment of seborrhoeic dermatitis.

The current application was aimed to evaluate the therapeutic potential of selenium and ketoconazole nanoparticles loaded hyaluronic acid gel against seborrhoeic dermatitis (SD). Amalgamation of ketoconazole (antifungal medication) and selenium (pro-oxidant) in an optimized formulation setting may help in the treatment of SD. In this study, selenium and ketoconazole nanoparticles loaded hyaluronic acid (HA) hydrogel was prepared by mechanical mixing followed by sonication. Results of the optimized batch showed a mean particle size of 121 ± 12 nm for ketoconazole and 51 ± 7 nm for selenium. SEM and TEM study revealed the prepared nanoparticles are of nanoscale dimension, with smooth spherical outline. Finally, the optimized nanoparticles were incorporated into HA hydrogel. Hydrogel exhibits desirable physical, mechanical and rheological characteristics appropriate for topical application. Optimized gel formulation exhibited an enhanced permeability with better antifungal, and anti-inflammatory activities, compared with the plain drug suspension. The optimized hydrogel with ketoconazole and selenium in nanotemplate could offer a potential strategy for the treatment of SD.

Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes' role overcome penetration enhancement effect?

The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers. Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml. Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions' interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ±â€¯0.2% for the MCT nanoemulsions, 13.9 ±â€¯0.1% and 14.0 ±â€¯0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.

Optimization and Evaluation of Beclomethasone Dipropionate Micelles Incorporated into Biocompatible Hydrogel Using a Sub-Chronic Dermatitis Animal Model.

The current study is concerned with the development and characterization of mixed micelles intended for the dermal delivery of beclomethasone dipropionate, which is a topical corticosteroid used in the management of atopic dermatitis. Mixed micelles were prepared using thin-film hydration technique, employing different concentrations of pluronic L121 with either poloxamer P84 or pluronic F127 with different surfactant mixture-to-drug ratios. The prepared formulae were characterized concerning entrapment efficiency, particle size, and zeta potential. Two formulae were chosen for ex vivo skin deposition studies: one formulated using pluronic L121/poloxamer P84 mixture while the other using pluronic L121/pluronic F127 mixture. The optimum formula with the highest dermal deposition was subjected to morphological examination and was formulated as hydroxypropyl methylcellulose hydrogel. The hydrogel was evaluated regarding viscosity and was subjected to ex vivo deposition study in comparison with the commercially available cream Beclozone®. In vivo histopathological study was conducted for both the hydrogel and Beclozone® in order to evaluate their healing efficiency. In vivo histopathological study results showed that the prepared hydrogel successfully treated sub-chronic dermatitis in an animal model within a shorter period of time compared to Beclozone®, resulting in better patient compliance and fewer side effects.

Synthesis and Characterization of Valacyclovir HCl Hybrid Solid Lipid Nanoparticles by Using Natural Oils.

BACKGROUND: The Jojoba Simmondsia Chinensis oil is used as one of the main ingredients which has an antioxidant, moisturizing and stabilizing activity. Likewise, grape seed (Vitis vinifera) oil is also used in this preparation which also has some remarkable medicinal properties such as antioxidant, astringent and is also used as a moisturizer. The Valacyclovir Solid Lipid Nanoparticles (SLN) are prepared in combination. OBJECTIVE: The prime objective of the study was to prepare a nanodispersion with good stability indicating zeta potential. The formulations were prepared by varying concentrations of jojoba oil and grape seed oil which form the hybrid nanoparticles with the drug. METHODS: The high-pressure hot-homogenization technique was used to prepare the nanoparticles. The prepared nanoparticles were subjected to characterization analysis such as Mean particle size, Zaverage, and Zeta potential by using Dynamic Light Scattering (DLS) and Photon Correlation Spectroscopy (PCS). The best formulation was subjected to Transmission Electron Microscopy (TEM) technique for surface morphology and other characterizations. The crystalline pattern of the drug alone, drug-loaded nanoparticles and nanoparticles without the drug was studied by XRD. The drug excipients compatibility studies were performed by using Fourier-Transform Infrared Spectroscopy (FTIR) Differential Scanning Calorimetry and (DSC). The other factors such as in vitro drug release, and % drug entrapment efficiency were studied by using suitable methods. RESULTS: The results demonstrated that the particles are in nano range with good stability with appreciable Zeta potential (-48.2±mV). The selected formulations were analyzed for MPS which demonstrated the value of 306.7±183.4 and 416.5±289.3. The best formulation VNP5 demonstrated the Bellshaped curve and confirmed the uniform distribution. CONCLUSION: Based on the patents, it was demonstrated that valacyclovir is widely used in the treatment and prophylaxis of viral infections in human, particularly infections caused by the herpes group of viruses. Valacyclovir is an effective drug for the treatment of cold sores.

Effect of Mild Hyperthermia on Transdermal Absorption of Nicotine from Patches.

Application of heat (hyperthermic conditions) on skin is known to enhance drug transfer and facilitate skin penetration of molecules. The aim of this work was to study the effect of hyperthermia on the drug release and skin permeation from nicotine transdermal patches. The drug release and skin permeation were characterized by in vitro release test and in vitro permeation test. The temperature was maintained at 32 °C as control (simulating normal physiological skin temperature) and 42 °C as hyperthermia condition. The in vitro release test was carried out using USP apparatus 5-Paddle over disk method for a transdermal patch. Skin permeation study was carried out across porcine skin using the flow through cells (PermeGear, Inc.) with an active diffusion area of 0.94 cm2. Mechanistic studies (parameters such as partition coefficient, TEWL and electrical resistivity) were also performed to understand the mechanisms involved in determining the influence of hyperthermia on drug delivery from transdermal patches of nicotine. The rate and extent of drug release from nicotine patch was not significantly different at two temperatures (Cumulative release after 12 h was 43.99 ± 3.29% at 32 °C and 53.70 ± 5.14% at 42 °C). Whereas, in case of in vitro permeation studies, the nicotine transdermal permeation flux for patch was threefold higher at 42 °C (100.1 ± 14.83 µg/cm2/h) than at 32 °C (33.3 ± 14.83 µg/cm2/h). The mechanistic studies revealed that the predominant mechanism of enhancement of drug permeation by hyperthermia condition is by the way of increasing the skin permeability. There is a potential concern of dumping of higher dose of nicotine via transdermal route.

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.

Skin Permeation and Oxidative Protection Effect of Soybean Isoflavones from Topical Nanoemulsions-a Comparative Study of Extracts and Pure Compounds.

Soybean isoflavone-rich extracts have been considered as promising skin antiaging products due to their antioxidant activity. This study investigates the effect of soybean isoflavone forms on porcine ear skin permeation/retention from topical nanoemulsions and their potential in protecting skin against oxidative damage caused by UVA/UVB light. Soybean non-hydrolyzed (SNHE) and hydrolyzed (SHE) extracts, mainly composed of genistin and genistein, were produced. Nanoemulsions containing SNHE (NESNHE) and SHE (NESHE) were prepared by spontaneous emulsification procedure and yielded monodispersed nanoemulsions. A delay of isoflavone release was observed after extracts incorporation into nanoemulsions when compared to a propyleneglycol dispersion of pure compounds. An increase of isoflavone skin retention from nanoemulsions was also achieved. However, from extracts, a higher amount of genistin (NESNHE) and a lower amount of genistein (NESHE) were detected in the skin in comparison to pure isoflavones. Finally, the protection of porcine ear skin by formulations against UVA/UVB oxidative stress was evaluated. Extract-loaded nanoemulsions offered better skin protection than pure isoflavones. Skin lipids were similarly protected by NESHE and NESNHE, whereas skin proteins were more protected by NESNHE. Overall, nanoemulsions containing isoflavone-rich soybean extracts may be considered a better topical formulation aiming skin protection from UVA/UVB oxidative damage.