Deeper Skin Layers Research Articles

High-Frequency Ultrasonography-Possibilities and Perspectives of the Use of 20 MHz in Teledermatology.

High-frequency ultrasonography (HF-USG) is a non-invasive and in vivo method of visualization of the skin and upper part of subcutaneous tissue based on ultrasounds above 20 MHz. Although initially HF-USG was introduced to measure skin thickness, it currently gained widespread acceptance in dermato-oncology, primarily when used to determine skin tumor margins. Moreover, its application in different dermatology fields is known, particularly as a rapidly evolving method in the objective evaluation of the severity of various chronic skin diseases. Among different specialties, teledermatology belongs to leading and continually developing areas of successful telemedicine applications. Various skin conditions are visible to the human eye, which makes them particularly suitable for telemedicine. However, HF-USG enables specialists to look into deeper skin layers, thus extending diagnostic options. On the other hand, teledermatology creates the possibility of sending images for consultation and facilitates the therapeutic decision as HF-USG can be used in an asynchronous store and forward manner. It seems that HF-USG and teledermatology may be regarded as a truly matched pair. The aim of this work is to present current applications of 20-MHz ultrasonography in dermatology, including skin neoplasms and chronic skin diseases. Moreover, the authors aimed to analyze the possibilities of HF-USG use as a valuable tool in teledermatology, especially in diagnosing and monitoring patients suffering from long-lasting skin conditions.

New Pickering emulsions stabilized with chitosan/collagen peptides nanoparticles: Synthesis, characterization and tracking of the nanoparticles after skin application

Pickering emulsions based on biopolymeric particles are gaining increasing research recognition in numerous applications due to their biocompatibility and eco-friendliness. In this work, chitosan/collagen peptides nanoparticles were applied to stabilize Pickering emulsions for potential cosmetic applications. The nanoparticles had a contact angle of 78.02° ± 2.04°, reflecting their hydrophilic nature. Their average size and zeta potential were 32.27 nm and +59.7 mV, respectively. Confocal laser scanning microscopy (CLSM) showed that the nanoparticles become well-adsorbed at the oil-water interface. The emulsions displayed shear-thinning viscosity and gel-like texture. Their average droplet size ranged between 7.63 μm and 15.72 μm. CLSM skin tracking of the nanoparticles, after ex vivo skin application of the Pickering emulsions, revealed the ability of the emulsion droplets to penetrate the stratum corneum and deposit in deeper skin layers. The penetration degree depends on the concentration of the nanoparticles in the emulsion and on the contact time with the skin. These results provide new insights into the fate of the nanoparticles used to stabilize Pickering emulsions following their skin application.

The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo.

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

Comparison of the antimicrobial efficacy of povidone-iodine-alcohol versus chlorhexidine-alcohol for surgical skin preparation on the aerobic and anaerobic skin flora of the shoulder region

BackgroundCutibacterium acnes is part of the anaerobic skin microbiome and resides in deeper skin layers. The organism is an agent of surgical site infections (SSI) in shoulder surgery. We hypothesized that prolonged skin preparation with an agent that penetrates deeply into the skin would be beneficial. Thus, we compared two classes of antiseptics, each combined with alcohol, each applied with two different contact times.MethodsUsing a cross-over arrangement, shoulders of 16 healthy volunteers were treated for 2.5 min (standard) or 30 min (prolonged) with alcohol-based chlorhexidine (CHG-ALC) or alcohol-based povidone-iodine (PVP-I-ALC). Skin sites were sampled before, immediately after, and 3 h after treatment, using a standardized cup-scrub technique.ResultsAerobic skin flora was reduced more effectively by PVP-I-ALC than by CHG-ALC after 2.5 min application and immediate sampling (reduction factor [RF] 2.55 ± 0.75 vs. 1.94 ± 0.91, p = 0.04), but not after prolonged contact times and 3-h sampling. Coagulase-negative staphylococci were completely eliminated after PVP-I-ALC application, but still recovered from 4 of 32 samples after CHG-ALC application. Anaerobic flora was reduced more effectively by PVP-I-ALC than CHG-ALC after standard (RF 3.96 ± 1.46 vs. 1.74 ± 1.24, p < 0.01) and prolonged (RF 3.14 ± 1.20 vs. 1.38 ± 1.16, p < 0.01) contact times and immediate sampling, but not after 3-h sampling. No adverse events were reported.ConclusionsPVP-I-ALC showed marginal benefits concerning the aerobic flora, but more substantial benefits over CHG-ALC concerning the anaerobic flora of the shoulder. Standard and prolonged contact times showed superiority for PVP-I-ALC for anaerobic flora at all immediate sampling points, but missed significance at 3-h sampling. The results underscore the need for protection against C. acnes and coagulase-negative staphylococci in orthopaedic surgery. The clinical relevance of these findings, however, should be studied with SSI as an endpoint.

Topical and transdermal delivery with diseased human skin: passive and iontophoretic delivery of hydrocortisone into psoriatic and eczematous skin.

Psoriasis and atopic dermatitis (eczema) are both common immune-mediated inflammatory skin diseases associated with changes in skin's stratum corneum lipid structure and barrier functionality. The present study aimed to investigate healthy, eczematous, and psoriatic excised human tissue for the effect of non-infectious skin diseases on skin characteristics (surface color, pH, transepidermal water loss, electrical resistance, and histology), as well as on permeation and retention profile of hydrocortisone. Further, differences in percutaneous absorption on application of iontophoresis on healthy and diseased skin were also investigated. Measurements of transepidermal water loss and electrical resistance showed a significant difference in psoriasis skin samples indicating a damaged barrier function. In vitro permeation studies on full-thickness human skin using vertical diffusion cells further confirmed these results as the drug amount retained in the psoriatic tissue was significantly higher when compared with the other groups. Despite no significant difference, the presence of the drug in the receptor chamber in both diseased groups can be concerning as it suggests the increased possibility of systemic absorption and adverse reactions associated with it in the use of topical corticosteroids. Application of anodal iontophoresis resulted in greater distribution of hydrocortisone into deeper layers of skin and the receptor chamber, in comparison to passive permeation. However, no significant differences were observed due to the healthy or diseased condition of skin.

Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: Determination of in vitro skin permeability and visualisation of dermal distribution

Chlorhexidine digluconate (CHG) is a cationic bisbiguanide used in the UK as the first-line skin antiseptic prior to surgery in the UK due to its favourable efficacy and safety profile, high affinity for skin binding and minimal reports of resistance. Despite this, bacteria remain within deeper skin layers, furrows and appendages that are considered inaccessible to CHG, due to its poor dermal penetration. In this study a third generation, polyamidoamine dendrimer (G3 PAMAM-NH2) was utilised to improve dermal penetration of CHG. A topical gel formulation was optimised to maximise CHG delivery (containing 0.5% gelling agent and 4% drug), followed by drug and dendrimer co-formulation into a commercially viable gel. The gel containing 4% CHG and 1 mM PAMAM dendrimer significantly increased the depth permeation of CHG compared to the commercial benchmark (Hibiscrub®, containing 4% w/v CHG) (p < 0.05). The optimised formulation was further characterised using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), which indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by commercial CHG formulations. This study therefore indicates that a G3 PAMAM-NH2 dendrimer gel may be viable as a permeation enhancer of CHG, for improved skin antisepsis in those at risk of a skin or soft tissue infection as a result of surgical intervention.

Thread Lifting of the Jawline: A Pilot Study for Quantitative Evaluation.

Introduction:The facial aging process produces changes that are characteristic of the superficial and deep fat framework and skin layers. Subdermal suspension with threads enables the sagging tissues to be lifted by means of a minimally invasive, closed procedure without surgical dissection. This observational study has been carried out on the basis of standardized tridimensional photographic analysis and measurement, aimed at determining objective, repetitive, and reliable evaluation of the soft tissue suspension technique.Materials and Methods:Eight participants were enrolled in this pilot study presenting with mild to moderate ptosis of the jawline tissues. Patient photographs were taken before (t0), immediately after threads implantation (t1), and at the following visit (t2). Each image captured before thread insertion was registered by the software and surface linear lengths in between the mentioned points were calculated.Results:The result showed an overall average improvement in the “tragus-to-marionette distance” (C-A) and the “tragus-to-jowl distance” after a mean follow-up time of 8.16 months (t0-t2). All analyzed parameters improved significantly (P < 0.05) at t1 and at t2 with respect to t0.Conclusions:This pilot study suggest that facial tissue suspension by means of poli-lactic/poli-caprolactone threads is safe and effective in treating skin flaws that affect mild-to-moderate ptosis of the jawline up to 8 months.

&lt;p&gt;Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention&lt;/p&gt;

BackgroundChallenges associated with local antibacterial and anti-inflammatory drugs include low penetration and retention of drugs at the expected action site. Additionally, improving these challenges allows for the prevention of side effects that are caused by drug absorption into the systemic circulation and helps to safely treat local skin diseases.MethodsIn the current study, we successfully prepared a thiolated pluronic F127 polymer micelles (BTFM), which binds to keratin through a disulphide bond, to produce skin retention. In addition, the small particle size of polymer micelles promotes the penetration of carriers into the skin. The current study was divided into two experiments: an in vitro experiment; an in vivo experiment that involved the penetration of the micelle-loaded drugs into the skin of rats, the skin irritation test and the anti-inflammatory activity of the drug-loaded micelles on dimethyl benzene-induced ear edema in mice.ResultsResults from our in vitro transdermal experiment revealed that the amount of drug absorbed through the skin was decreased after the drug was loaded in the BTFM. Further, results from the vivo study, which used fluorescence microscopy to identify the location of the BTFM after penetration, revealed that there was strong fluorescence in the epidermis layer, but there was no strong fluorescence in the deep skin layer. In addition, the BTFM had a very good safety profile with no potentially hazardous skin irritation and transdermal administration of BTFM could significantly suppress ear edema induced by dimethyl benzene. Therefore, these findings indicated that BTFM reduced the amount of drug that entered the systemic circulation. Our results also demonstrated that the BTFM had a certain affinity for keratin.ConclusionOur experimental results suggest that the BTFM may be an effective drug carrier for local skin therapy with good safety profile.

Targeting of the Pilosebaceous Follicle by Liquid Crystal Nanocarriers: In Vitro and In Vivo Effects of the Entrapped Minoxidil.

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.

Microneedles mediated bioinspired lipid nanocarriers for targeted treatment of alopecia

Microneedles deliver bioinspired lipid nanocarriers of FIN (FIN-NLC) to the deep skin layer, and FIN-NLC further specifically delivers FIN to hair follicles to promote hair growth in androgenetic alopecia. • Designed microneedles with finasteride nanostructured lipid carriers (FIN-NLC-MNs) • Enhanced FIN targeting to the hair follicles using bioinspired NLC • Improved hair growth, anagen restoration, and gene regulation by FIN-NLC-MNs • Combined NLC and MNs synergistically enhance skin penetration and anti-alopecia. • The strategy represents a promising drug delivery system for androgenetic alopecia.

The Challenge of Nanovesicles for Selective Topical Delivery for Acne Treatment: Enhancing Absorption Whilst Avoiding Toxicity.

Acne is a common skin disease that affect over 80% of adolescents. It is characterized by inflammation of the hair bulb and the attached sebaceous gland. To date, many strategies have been used to treat acne as a function of the disease severity. However, common treatments for acne seem to show several side effects, from local irritation to more serious collateral effects. The use of topical vesicular carriers able to deliver active compounds is currently considered as an excellent approach in the treatment of different skin diseases. Many results in the literature have proven that drug delivery systems are useful in overcoming the toxicity induced by common drug therapies, while maintaining their therapeutic efficacy. Starting from these assumptions, the authors reviewed drug delivery systems already realized for the topical treatment of acne, with a focus on their limitations and advantages over conventional treatment strategies. Although their exact mechanism of permeation is not often completely clear, deformable vesicles seem to be the best solution for obtaining a specific delivery of drugs into the deeper skin layers, with consequent increased local action and minimized collateral effects.

Target action of antioxidants using iontophoresis.

The use of antioxidants in applications for topical use seems promising, however, many studies must be performed to ensure processes and products that can effectively bring benefits to combat the action of free radicals in the skin. For topical antioxidants to be effective against free radicals from the skin, it is essential that the antioxidants compounds permeate the different skin layers, to reach deeper layers of the epidermis in active form and stay there for a sufficient time to cause the beneficial effects. This work aimed to evaluate the antioxidant action of formulations with phenolic compounds as well as to comprehend the skin retention profile of these actives. The antioxidant potential was recognized with isolated phenolic acids (gallic, caffeic, and ferulic acid) or in combinations, using different in vitro methods (DPPH ABTS , FRAP , β-carotene/linoleic acid system and ORAC). The skin retention study was performed through in vitro assay with Franz's diffusion cell associating, or not, the cathodic iontophoresis. Gallic acid showed the greatest antioxidant activity and was selected for a study of skin permeation following gel application to porcine skin, with or without cathodic iontophoresis. Gallic acid retention in deeper skin layers was promoted by iontophoresis, and increased skin antioxidant activity was detected after only 20 min of iontophoresis. The present study demonstrated the importance of polymeric gelling agents for optimizing the antioxidant activity. The cathodic iontophoresis represents a promising strategy to promote a target action of antioxidants in the skin.

Efficacy and Safety of Laser-Assisted Combination Chemotherapy: An Explorative Imaging-Guided Treatment With 5-Fluorouracil and Cisplatin for Basal Cell Carcinoma.

Rising incidences of basal cell carcinoma (BCC) have increased the need for effective topical therapies. By enhancing cutaneous uptake of the chemotherapeutic agents, cisplatin and 5-fluorouracil (5-FU), laser-assisted delivery may provide a new combination treatment for BCC. Accordingly, this study aimed to evaluate tumor response, safety, and drug biodistribution in tumors and blood after topical laser-assisted 5-FU + CIS treatment in BCC patients. This open-label, proof-of-concept trial investigated laser-assisted combination cisplatin + 5-FU treatment in 20 patients with histologically verified, low-risk superficial or nodular BCCs on the face (<20 mm) or trunk/extremities (<50 mm). After tumor demarcation guided by optical coherence tomography (OCT), BCCs were exposed to ablative fractional CO2 laser followed by 60 minutes topical cisplatin solution and 7-day exposure to 5% 5-FU cream under occlusion. After 30 days, treatment was repeated if any tumor residual was identified. Tumor response at day 30 and month 3 was assessed clinically as well as by OCT, reflectance confocal microscopy, and ultrasound, supplemented by histological verification at 3 months. Local skin reactions (LSRs) and side effects were evaluated on days 1, 3-5, 14, 30, and month 3. Drug detection in tumors and blood was performed in a subset of patients 1- and 24 hours after treatment. Nineteen patients completed the trial, with 32% (6/19) receiving a single treatment and 68% (13/19) treated twice. At 3 months, clinical clearance was seen in 18/19 patients with a corresponding 94% (17/18) achieving histological clearance. Baseline tumor thickness and subtype did not influence treatment number or clearance rate (P ≥ 0.61). LSRs were well-tolerated and consisted of erythema, edema, and erosion, followed by crusting by day 14. Erythema declined gradually by month 3, with 94% of patients and 79% of physicians rating cosmesis as "good" or "excellent." Scarring or hyperpigmentation was noted in 50% and 56%, respectively, while pain and infection were not observed during the follow-up period. Although chemotherapy uptake was visualized extending to deep skin layers, no systemic exposure to cisplatin or 5-FU was detected in patient blood. Laser-assisted cisplatin + 5-FU shows potential as an effective and tolerable treatment option for low-risk BCC, particularly in instances where self-application is not possible or where in-office, non-surgical therapy is preferred. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Ionic liquids containing ketoconazole improving topical treatment of T. Interdigitale infection by synergistic action

This study aimed to exert the synergistic action of ketoconazole (KCZ) and ionic liquids (ILs) for improving antifungal effect. Various ILs were engineered and demonstrated different solubilization capacity for KCZ. Among them, the IL formed by choline and geranic acid ([Ch][Ger]) was the optimal one and able to imporve the solubility of KCZ by around 100-fold. The in vitro antifungal test revealed the [Ch][Ger] significantly inhibited the activity of T. Interdigitale and exerted the synergistic action with KCZ. Compared to Daktarin®, the [Ch][Ger] not only promoted KCZ to penetrate into deep skin layer but also improved in vivo anti-T. Interdigitale activity significantly. Besides, the [Ch][Ger] was able to strip the skin of the lesion site in a flaky manner to remove fungi more thoroughly. However, the skin can recover to be normal state after treatment and there was no evident skin irritation found in [Ch][Ger] group. The ILs may offer promising opportunities to deliver anti-fungal drugs to treat inner skin fungal infections by synergistic action.

Preliminary Assays towards Melanoma Cells Using Phototherapy with Gold-Based Nanomaterials.

Cancer like melanoma is a complex disease, for which standard therapies have significant adverse side effects that in most cases are ineffective and highly unspecific. Thus, a new paradigm has come with the need of achieving alternative (less invasive) and effective therapies. In this work, biocompatible gold nanoparticles (GNPs) coated with hyaluronic acid and oleic acid were prepared and characterized in terms of size, morphology and cytotoxicity in the presence of Saccharomyces cerevisiae, and two cell lines, the keratinocytes (healthy skin cells, HaCat) and the melanoma cells (B16F10). Results showed that these GNPs absorb within the near-infrared region (750–1400 nm), in the optical therapeutic window (from 650 to 1300 nm), in contrast to other commercial gold nanoparticles, which enables light to penetrate into deep skin layers. A laser emitting in this region was applied and its effect also analyzed. The coated GNPs showed a spherical morphology with a mean size of 297 nm without cytotoxic effects towards yeast and tested cell lines. Nevertheless, after laser irradiation, a reduction of 20% in B16F10 cell line viability was observed. In summary, this work appears to be a promising strategy for the treatment of non-metastatic melanoma or other superficial tumors.

Stabilization of ferulic acid in topical gel formulation via nanoencapsulation and pH optimization

Ferulic acid is a potent anti-oxidant with scientifically proven skin care efficacies. However, instability of this active in the skin care products restricted its wide application in beauty and skin care industries. This study aimed to stabilize ferulic acid in topical hydrogel formulation via nanoencapsulation technique. Ferulic acid loaded nanocapsules were prepared via high pressure homogenization method and physicochemically characterized. Mean particle size of ferulic acid loaded nanocapsules was < 300 nm. TEM and SEM images exhibited spherical particles with smooth surface. DSC and XRD results indicated that ferulic acid was completely dissolved in the lipid matrix of the nanocapsules and remained in amorphous form. Two types of hydrogel formulations containing ferulic acid loaded nanocapsules were prepared: Gel A with pH higher and Gel B with pH lower than pKa of ferulic acid. Cross-polarized microscopic image of the gel formulations did not show presence of any un-encapsulated and un-dissolved crystal. Gel B showed slower and controlled release of ferulic acid than Gel A. Ferulic acid permeation through skin mimic from the gel formulation demonstrated controlled permeation. Color stability of the gel and chemical stability of ferulic acid were very good in Gel B, while poor in Gel A (although significantly better than the gel with un-encapsulated ferulic acid). The result clearly indicates that together with nanoencapsulation, low pH (less than pKa of ferulic acid) of the hydrogel was crucial for both product appearance and chemical stability of ferulic acid. In fact, it has been proved that skin care product with low pH is good for skin as it can maintain skin homeostasis and microbiome. Furthermore, the permeation result suggests that ferulic acid may penetrate into deep skin layers and at the same time avoid systemic circulation. Overall, this low pH hydrogel formulation containing nanoencapsulated ferulic acid demonstrates great promise for commercialization.

Profiling of drug crystallization in the skin

ABSTRACT Background Drug crystallization following application of transdermal and topical formulations may potentially compromise the delivery of drugs to the skin. This phenomenon was found to be limited to the superficial layers of the stratum corneum (~7 µm) in our recent reports and tape stripping of the skin samples was necessary. It remains a significant challenge to profile drug crystallization in situ without damaging the skin samples. Methods This work reports the application of an X-ray microbeam via synchrotron SAXS/WAXS analysis to monitor drug crystallization in the skin, especially in the deeper skin layers. Confocal Raman spectroscopy (CRS) was employed to examine drug distribution in the skin to complement the detection of drug crystallization using SAXS/WAXS analysis. Results Following application of saturated drug solutions (ibuprofen, diclofenac acid, and salts), CRS depth profiles confirmed that the drugs generally were delivered to a depth of ~15 – 20 µm in the skin. This was compared with the WAXS profiles that measured drug crystal diffraction at a depth of up to ~25 µm of the skin. Conclusion This study demonstrates the potential of synchrotron SAXS/WAXS analysis for profiling of drug crystallization in situ in the deeper skin layers without pre-treatment for the skin samples.

A facile fabrication of dissolving microneedles containing 5-aminolevulinic acid.

Photodynamic therapy induced by protoporphyrin IX (PpIX) is widely used to treat precancerous skin lesions. The penetration depth of the prodrug 5-aminolevulinic acid (5-ALA) using topical application is currently limited, which hampers the production of PpIX in deep seated lesions. To enhance 5-ALA delivery in deep skin layers, a soluble microneedles patch (MN-patch) containing 5-ALA has been successfully developed by using a fast solvent casting molding method which could be easily up-scaled. The shape, number and height of the needles have been designed according to the medical application and the mechanical strain necessary for skin insertion. Hyaluronic acid (HA) has been chosen as the needle materials due to its biocompatibility, fast solubility and biodegradation and was mixed with 5-ALA prior to casting. HA-based MN-patch containing 5-ALA have exhibited mechanical properties enabling a good insertion into the skin without significant damages to MN. Interactions between HA and 5-ALA were evaluated by Fourier transform infrared spectroscopy (FTIR) and carbon nuclear magnetic resonance (13C NMR), stability of 5-ALA in the MN-patch was monitored by proton nuclear magnetic resonance (1H NMR) and exhibited a good stability over 5 months after manufacturing. Dissolution rate of the whole patch was completed in 1 hour in ex vivo rat skin without cytotoxicity. Overall, the MN-patch can be a promising technique to enhance 5-ALA penetration and produce PpIX in deeper skin lesions.

The Development of Phyllanthus emblica Extract in Ethosomes for Hair Loss Prevention

Background: Hair loss is not a serious health problem but leads to decreased self- confidence, personality, and psychological problems. According to Thai traditional medical wisdom, Phyllanthus emblica has the property to prevent hair loss. Ethosomes are a drug delivery system, which can increase drug delivery to deep skin layers and enhance the effectiveness of the active ingredient. Objective: This research aims to develop ethosomes of Phyllanthus emblica extract with beneficial properties. Materials and Methods: Phyllanthus emblica was extracted by a maceration method with 95% ethanol as a solvent. The total phenolic content of the extracts was determined using the Folin-Ciocalteu method. The antioxidation activity was evaluated by DPPH assay. Ethosomes were formulated by a cold method and their properties were observed. Results: The results showed that the total phenolic content of Phyllanthus emblica extract was 406.37±2.39 mg GAE/g extract. The IC50 of antioxidant activity was 7.05±0.17 μg/ml. Ethosomes with 0.03% of Phyllanthus emblica extract, 2% of soya phosphatidylcholine, and 20% of ethanol had the highest percentage of entrapment efficiency (65.26%±1.80%). The ethosomes of Phyllanthus emblica extract was the spherical shape and white colloid. The particle size, polydispersity index, zeta potential, and pH of ethosomes were 0.43±0.00 μm, 0.44±0.03, -10.40±0.28 mV, and 4.06±0.03, respectively. Conclusion: The ethosomes of Phyllanthus emblica extract had good properties and area possible alternative product for hair loss prevention.

Microemulsion composed of combination of skin beneficial oils as vehicle: Development of resveratrol-loaded microemulsion based formulations for skin care applications

Microemulsion can be a potential delivery vehicle to deliver skin care actives to deep skin layer for chronic skin care benefits. On top of skin care active, microemulsion vehicle composed of multiple skin beneficial oils can deliver additional skin care efficacies. In this study, microemulsions were developed using combinations of two skin beneficial oils, tea tree oil and medium chain triglyceride instead of single oil. For that, pseudo ternary phase diagrams were constructed on these oil combinations at different ratios of surfactant/co-surfactants. Ratio of oils and surfactant/co-surfactant combinations exhibited significant impact on the microemulsion region. A few compositions were selected from the single phase microemulsion regions of these phase diagrams for the preparation of resveratrol-loaded microemulsion and microemulsion gel formulations. The particle size of the resveratrol-loaded microemulsions were <50 nm. Cryogenic scanning electron microscope image clearly showed nano-droplets dispersed in continuous phase. Both physical and chemical stability of the formulations varied depending on their compositions, such as surfactant/co-surfactant combination and % total oil. The presence of chelating agent and anti-oxidant was also crucial to stabilize the formulations. The selected formulations demonstrated good physicochemical stability at 5 °C, 25 °C, and 40 °C/75 % RH (relative humidity) stability conditions. The results further showed that the % total oil and surfactant phase composition had huge influence on resveratrol release and skin permeation patterns from the microemulsion gels. In vitro skin permeation result indicated that the microemulsion gels can help resveratrol penetration into deep skin layer. Therefore, the developed resveratrol-loaded microemulsion gels can be utilized as skin care product with multiple skin care benefits.