Enhanced chlorhexidine skin penetration with eucalyptus oil

PubMed Central

2010-01-01

Background Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic. Method Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (μg/mg of skin) was determined to a skin depth of 1500 μm by high performance liquid chromatography (HPLC). Results The 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min. Conclusion The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis. PMID:20860796

Penetration of silver nanoparticles into porcine skin ex vivo using fluorescence lifetime imaging microscopy, Raman microscopy, and surface-enhanced Raman scattering microscopy.

PubMed

Zhu, Yongjian; Choe, Chun-Sik; Ahlberg, Sebastian; Meinke, Martina C; Alexiev, Ulrike; Lademann, Juergen; Darvin, Maxim E

2015-05-01

In order to investigate the penetration depth of silver nanoparticles (Ag NPs) inside the skin, porcine ears treated with Ag NPs are measured by two-photon tomography with a fluorescence lifetime imaging microscopy (TPT-FLIM) technique, confocal Raman microscopy (CRM), and surface-enhanced Raman scattering (SERS) microscopy. Ag NPs are coated with poly-N-vinylpyrrolidone and dispersed in pure water solutions. After the application of Ag NPs, porcine ears are stored in the incubator for 24 h at a temperature of 37°C. The TPT-FLIM measurement results show a dramatic decrease of the Ag NPs' signal intensity from the skin surface to a depth of 4 μm. Below 4 μm, the Ag NPs' signal continues to decline, having completely disappeared at 12 to 14 μm depth. CRM shows that the penetration depth of Ag NPs is 11.1 ± 2.1 μm. The penetration depth measured with a highly sensitive SERS microscopy reaches 15.6 ± 8.3 μm. Several results obtained with SERS show that the penetration depth of Ag NPs can exceed the stratum corneum (SC) thickness, which can be explained by both penetration of trace amounts of Ag NPs through the SC barrier and by the measurements inside the hair follicle, which cannot be excluded in the experiment.

Topical dissolved oxygen penetrates skin: model and method.

PubMed

Roe, David F; Gibbins, Bruce L; Ladizinsky, Daniel A

2010-03-01

It has been commonly perceived that skin receives its oxygen supply from the internal circulation. However, recent investigations have shown that a significant amount of oxygen may enter skin from the external overlying surface. A method has been developed for measuring the transcutaneous penetration of human skin by oxygen as described herein. This method was used to determine both the depth and magnitude of penetration of skin by topically applied oxygen. An apparatus consisting of human skin samples interposed between a topical oxygen source and a fluid filled chamber that registered changes in dissolved oxygen. Viable human skin samples of variable thicknesses with and without epidermis were used to evaluate the depth and magnitude of oxygen penetration from either topical dissolved oxygen (TDO) or topical gaseous oxygen (TGO) devices. This model effectively demonstrates transcutaneous penetration of topically applied oxygen. Topically applied dissolved oxygen penetrates through >700 microm of human skin. Topically applied oxygen penetrates better though dermis than epidermis, and TDO devices deliver oxygen more effectively than TGO devices. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Skin Penetration Enhancement by Natural Oils for Dihydroquercetin Delivery.

PubMed

Čižinauskas, Vytis; Elie, Nicolas; Brunelle, Alain; Briedis, Vitalis

2017-09-12

Natural oils are commonly used in topical pharmaceutical formulations as emulsifiers, stabilizers or solubility enhancers. They are presented as safe and inert components, mainly used for formulation purposes. It is confirmed that natural oils can affect the skin penetration of various substances. Fatty acids are mainly responsible for this effect. Current understanding lacks reliable scientific data on penetration of natural oils into the skin and their skin penetration enhancement potential. In the current study, fatty acid content analysis was used to determine the principal fatty acids in soybean, olive, avocado, sea-buckthorn pulp, raspberry seed and coconut oils. Time of flight secondary ion mass spectrometry bioimaging was used to determine the distribution of these fatty acids in human skin ex vivo after application of the oils. Skin penetration enhancement ratios were determined for a perspective antioxidant compound dihydroquercetin. The results demonstrated skin penetration of fatty acids from all oils tested. Only soybean and olive oils significantly increased the skin distribution of dihydroquercetin and can be used as skin penetration enhancers. However, no correlation can be determined between the fatty acids' composition and skin penetration enhancement using currently available methodological approaches. This indicates that potential chemical penetration enhancement should be evaluated during formulation of topically applied products containing natural oils.

Advanced imaging approaches for characterizing nanoparticle delivery and dispersion in skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prow, Tarl W.; Yamada, Miko; Dang, Nhung; Evans, Conor L.

2017-02-01

The purpose of this research was to develop advanced imaging approaches to characterise the combination of elongated silica microparticles (EMP) and nanoparticles to control topical delivery of drugs and peptides. The microparticles penetrate through the epidermis and stop at the dermal-epidermal junction (DEJ). In this study we incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into the nanoparticle for visualization with microscopy. In another nanoparticle-based approach we utilized a chemically functionalized melanin nanoparticle for peptide delivery. These nanoparticles were imaged by coherent anti-Stoke Raman scattering (CARS) microscopy to characterize the delivery of these nanoparticles into freshly excised human skin. We compared four different coating approaches to combine EMP and nanoparticles. These data showed that a freeze-dried formulation with cross-linked alginate resulted in 100% of the detectable nanoparticle retained on the EMP. When this dry form of EMP-nanoparticle was applied to excised, living human abdominal skin, the EMP penetrated to the DEJ followed by controlled release of the nanoparticles. This formulation resulted in a sustained release profile, whereas a freeze-dried formulation without crosslinking showed an immediate burst-type release profile. These data show that advanced imaging techniques can give unique, label free data that shows promise for clinical investigations.

Vehicle effects on human stratum corneum absorption and skin penetration.

PubMed

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.

PubMed

Li, Li; ten Hagen, Timo L M; Bolkestein, Michiel; Gasselhuber, Astrid; Yatvin, Jeremy; van Rhoon, Gerard C; Eggermont, Alexander M M; Haemmerich, Dieter; Koning, Gerben A

2013-04-28

Accumulation of nanoparticles in solid tumors depends on their extravasation. However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery. Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow. The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models. Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~85 nm) accumulation by intravital confocal microscopy. Local hyperthermia at 41°C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models. A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration. After hyperthermia, the tumor vasculature remains permeable for 8h. We visualize gaps in the endothelial lining of up to 10 μm induced by HT. Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27.5 μm in radius from the vessel walls. Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia. In conclusion, a thermal dose of 41°C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration. These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

The isolated perfused human skin flap model: A missing link in skin penetration studies?

PubMed

Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

2017-01-01

Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoinduced Disaggregation of TiO2 Nanoparticles Enables Transdermal Penetration

PubMed Central

Bennett, Samuel W.; Zhou, Dongxu; Mielke, Randall; Keller, Arturo A.

2012-01-01

Under many aqueous conditions, metal oxide nanoparticles attract other nanoparticles and grow into fractal aggregates as the result of a balance between electrostatic and Van Der Waals interactions. Although particle coagulation has been studied for over a century, the effect of light on the state of aggregation is not well understood. Since nanoparticle mobility and toxicity have been shown to be a function of aggregate size, and generally increase as size decreases, photo-induced disaggregation may have significant effects. We show that ambient light and other light sources can partially disaggregate nanoparticles from the aggregates and increase the dermal transport of nanoparticles, such that small nanoparticle clusters can readily diffuse into and through the dermal profile, likely via the interstitial spaces. The discovery of photoinduced disaggregation presents a new phenomenon that has not been previously reported or considered in coagulation theory or transdermal toxicological paradigms. Our results show that after just a few minutes of light, the hydrodynamic diameter of TiO2 aggregates is reduced from ∼280 nm to ∼230 nm. We exposed pigskin to the nanoparticle suspension and found 200 mg kg−1 of TiO2 for skin that was exposed to nanoparticles in the presence of natural sunlight and only 75 mg kg−1 for skin exposed to dark conditions, indicating the influence of light on NP penetration. These results suggest that photoinduced disaggregation may have important health implications. PMID:23155401

Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid)

PubMed Central

Yu, Tao; Wang, Ying-Ying; Yang, Ming; Schneider, Craig; Zhong, Weixi; Pulicare, Sarah; Choi, Woo-Jin; Mert, Olcay; Fu, Jie; Lai, Samuel K.; Hanes, Justin

2013-01-01

Mucus secretions coating entry points to the human body that are not covered by skin efficiently trap and clear conventional drug carriers, limiting controlled drug delivery at mucosal surfaces. To overcome this challenge, we recently engineered nanoparticles that readily penetrate a variety of human mucus secretions, which we termed mucus-penetrating particles (MPP). Here, we report a new biodegradable MPP formulation based on diblock copolymers of poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA-PEG). PLGA-PEG nanoparticles prepared by a solvent diffusion method rapidly diffused through fresh, undiluted human cervicovaginal mucus (CVM) with an average speed only eightfold lower than their theoretical speed in water. In contrast, PLGA nanoparticles were slowed more than 12,000-fold in the same CVM secretions. Based on the measured diffusivities, as much as 75% of the PLGA-PEG nanoparticles are expected to penetrate a 10-μm-thick mucus layer within 30 min, whereas virtually no PLGA nanoparticles are expected to do so over the same duration. These results encourage further development of PLGA-PEG nanoparticles as mucus-penetrating drug carriers for improved drug and gene delivery to mucosal surfaces. PMID:24205449

Penetration through the Skin Barrier.

PubMed

Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

2016-01-01

The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates. During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients. This has stimulated research in methods for sampling, measuring and predicting percutaneous penetration. Previous chapters have described how different endogenous, genetic and exogenous factors may affect barrier characteristics. The present chapter introduces the theory for barrier penetration (Fick's law), and describes and discusses different methods for measuring the kinetics of percutaneous penetration of chemicals, including in vitro methods (static and flow-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous penetration. Finally, a short discussion of the advantages and challenges of each method is provided, which will hopefully allow the reader to improve decision making and treatment planning, as well as the evaluation of experimental studies of percutaneous penetration of chemicals. © 2016 S. Karger AG, Basel.

Programmed Nanoparticle-Loaded Nanoparticles for Deep-Penetrating 3D Cancer Therapy.

PubMed

Kim, Jinhwan; Jo, Changshin; Lim, Won-Gwang; Jung, Sungjin; Lee, Yeong Mi; Lim, Jun; Lee, Haeshin; Lee, Jinwoo; Kim, Won Jong

2018-05-18

Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting "nanoparticle-loaded nanoparticles" to address the long-lasting problem is reported for effective surface-to-core drug delivery in entire 3D tumors. The "nanoparticle-loaded nanoparticle" is a silica nanoparticle (≈150 nm) with well-developed, interconnected channels (diameter of ≈30 nm), in which small gold nanoparticles (AuNPs) (≈15 nm) with programmable DNA are located. The nanoparticle (AuNPs)-loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface-to-core tumor tissues, and finally (3) release a drug triggered by cancer-characteristic pH gradients. The hierarchical "nanoparticle-loaded nanoparticle" can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effectiveness of hand washing on the removal of iron oxide nanoparticles from human skin ex vivo.

PubMed

Lewinski, Nastassja A; Berthet, Aurélie; Maurizi, Lionel; Eisenbeis, Antoine; Hopf, Nancy B

2017-08-01

In this study, the effectiveness of washing with soap and water in removing nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (α-Fe 2 O 3 ) or maghemite (γ-Fe 2 O 3 ) powder, with primary particle diameters between 20-30 nm, were applied to two samples each of fresh and frozen ex vivo human skin in two independent experiments. The permeation of nanoparticles through skin, and the removal of nanoparticles after washing with soap and water were investigated. Bare iron oxide nanoparticles remained primarily on the surface of the skin, without penetrating beyond the stratum corneum. Skin exposed to iron oxide nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively, of the original dose after washing. In the event of dermal exposure to chemicals, removal is essential to avoid potential local irritation or permeation across skin. Although manufactured at an industrial scale and used extensively in laboratory experiments, limited data are available on the removal of engineered nanoparticles after skin contact. Our finding raises questions about the potential consequences of nanoparticles remaining on the skin and whether alternative washing methods should be proposed. Further studies on skin decontamination beyond use of soap and water are needed to improve the understanding of the potential health consequences of dermal exposure to nanoparticles.

Penetration of ASM 981 in canine skin: a comparative study.

PubMed

Gutzwiller, Meret E Ricklin; Reist, Martin; Persohn, Elke; Peel, John E; Roosje, Petra J

2006-01-01

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

NASA Astrophysics Data System (ADS)

Wang, Huan-Lei; Fan, Peng-Fei; Guo, Xia-Sheng; Tu, Juan; Ma, Yong; Zhang, Dong

2016-12-01

Transdermal drug delivery (TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid (HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers (e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents (UCAs). When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications (e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful. Project partially supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 81473692, 81673995, 11374155, 11574156, 11274170, 11274176, 11474001

Is skin penetration a determining factor in skin sensitization ...

EPA Pesticide Factsheets

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW 1 is a true requirement for sensitisation.Methods. A large dataset of substances that had been evaluated for their skin sensitisation potential, together with measured LogKow values was compiled from the REACH database. The incidence of skin sensitisers relative to non-skin sensitisers below and above the LogKow = 1 threshold was evaluated. Results. 1482 substances with associated skin sensitisation outcomes and measured LogKow values were identified. 305 substances had a measured LogKow < 0 and of those, 38 were sensitisers.Conclusions. There was no significant difference in the incidence of skin sensitisation above and below the LogKow = 1 threshold. Reaction chemistry considerations could explain the skin sensitisation observed for the 38 sensitisers with a LogKow < 0. The LogKow threshold is a self-evident truth borne out from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of skin sensitisation potential and potency. Using the REACH data extracted to test out the validity of common assumptions in the skin sensitization AOP. Builds on trying to develop a proof of concept IATA

Fractional laser microablation of skin aimed at enhancing its permeability for nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genina, Elina A; Dolotov, L E; Bashkatov, A N

2011-05-31

A new method for delivering nanoparticles into the skin using the fractional laser microablation of its surface and the ultrasonic treatment is proposed. As a result of in vitro and in vivo studies, it is shown that the 290-nm laser pulses with the energy from 0.5 to 3.0 J provide the penetration of nanoparticles of titanium dioxide with the diameter {approx}100 nm from the skin surface to the depth, varying from 150 to 400 {mu}m. Histological testing of the skin areas, subjected to the treatment, shows that the particles stay in the dermis at the depth up to 400 {mu}mmore » no less than for three weeks. (optical technologies in biophysics and medicine)« less

Comparison of the Skin Penetration of 3 Metabolically Stable Chemicals Using Fresh and Frozen Human Skin.

PubMed

Jacques-Jamin, Carine; Duplan, Hélène; Rothe, Helga; Vaillant, Ophelie; Eilstein, Joan; Grégoire, Sebastien; Cubberley, Richard; Lange, Daniela; Ellison, Corie; Klaric, Martina; Hewitt, Nicola; Schepky, Andreas

2017-01-01

The Cosmetics Europe ADME Task Force is developing in vitro and in silico tools for predicting skin and systemic concentrations after topical application of cosmetic ingredients. There are conflicting reports as to whether the freezing process affects the penetration of chemicals; therefore, we evaluated whether the storage of human skin used in our studies (8-12 weeks at -20°C) affected the penetration of model chemicals. Finite doses of trans-cinnamic acid (TCA), benzoic acid (BA), and 6-methylcoumarin (6MC) (non-volatile, non-protein reactive and metabolically stable in skin) were applied to fresh and thawed frozen skin from the same donors. The amounts of chemicals in different skin compartments were analysed after 24 h. Although there were some statistical differences in some parameters for 1 or 2 donors, the penetration of TCA, BA, and 6MC was essentially the same in fresh and frozen skin, i.e., there were no biologically relevant differences in penetration values. Statistical differences that were evident indicated that penetration was marginally lower in frozen than in fresh skin, indicating that the barrier function of the skin was not lost. The penetration of the 3 chemicals was essentially unaffected by freezing the skin at -20°C for up to 12 weeks. © 2017 S. Karger AG, Basel.

Topically applied hypericin exhibits skin penetrability on nude mice.

PubMed

Li, Zhuo-Heng; Li, Yuan-Yuan; Hou, Min; Yang, Tao; Lu, Lai-Chun; Xu, Xiao-Yu

2018-06-13

Hypericin, a powerful natural photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of topically applied hypericin, expecting a reduced risk of prolonged skin photosensitivity, which often occurs after systemic administration. Firstly, the Franz diffusion cell assays were performed to evaluate the penetration effects of different enhancers, including menthol, propylene glycol, camphanone, azone, and carbamide. In view of above evaluation results, we selected menthol as the enhancer in the subsequent in vivo studies. The setting groups were as follows: the blank control group, the light-exposure control group, the gel-base control group, the hypericin gel group, and a hypericin gel-containing menthol group. Except for the blank control, all other animals were irradiated by a LED light. Then, fluorescence microscopy was performed to examine the distribution of hypericin in the skin of nude mouse. Macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression change of PECAM-1. As shown in the results, menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mouse skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin-PDT treatment was replaced by normal skin within 7 days. We concluded that topical applied hypericin could penetrate nude mouse skin well and has a great potential in PDT treatment of skin diseases.

Evaluation of nicotinamide microemulsion on the skin penetration enhancement.

PubMed

Boonme, Prapaporn; Boonthongchuay, Chalida; Wongpoowarak, Wibul; Amnuaikit, Thanaporn

2016-01-01

This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4 °C and room temperature (≈30 ± 2 °C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.

A custom tailored model to investigate skin penetration in porcine skin and its comparison with human skin.

PubMed

Herbig, Michael E; Houdek, Pia; Gorissen, Sascha; Zorn-Kruppa, Michaela; Wladykowski, Ewa; Volksdorf, Thomas; Grzybowski, Stephan; Kolios, Georgios; Willers, Christoph; Mallwitz, Henning; Moll, Ingrid; Brandner, Johanna M

2015-09-01

Reliable models for the determination of skin penetration and permeation are important for the development of new drugs and formulations. The intention of our study was to develop a skin penetration model which (1) is viable and well supplied with nutrients during the period of the experiment (2) is mimicking human skin as far as possible, but still is independent from the problems of supply and heterogeneity, (3) can give information about the penetration into different compartments of the skin and (4) considers specific inter-individual differences in skin thickness. In addition, it should be quick and inexpensive (5) and without ethical implications (6). Using a chemically divers set of four topically approved active pharmaceutical ingredients (APIs), namely diclofenac, metronidazole, tazarotene, and terbinafine, we demonstrated that the model allows reliable determination of drug concentrations in different layers of the viable epidermis and dermis. For APIs susceptible for skin metabolism, the extent of metabolic transformation in epidermis and dermis can be monitored. Furthermore, a high degree of accordance in the ability for discrimination of skin concentrations of the substances in different layers was found in models derived from porcine and human skin. Viability, proliferation, differentiation and markers for skin barrier function were surveyed in the model. This model, which we call 'Hamburg model of skin penetration' is particularly suited to support a rational ranking and selection of dermatological formulations within drug development projects. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro human skin penetration of geraniol and citronellol.

PubMed

Gilpin, Sarah; Hui, Xiaoying; Maibach, Howard

2010-01-01

Geraniol and citronellol are commonly used fragrance components in consumer products. Both are listed as alleged fragrance allergens that should be declared in the European Union when used in cosmetics and consumer products. Such allergenic potential is determined largely by effects on the skin once these materials penetrate and elicit an immune response. Few data demonstrate their penetration abilities or their effects on percutaneous absorption. We wanted to determine the effects of these materials on skin absorption. Skin penetration characterization via flow-through diffusion study serves as a reasonable model for determining dermal dosing for fragrance materials. Such characterization can be used for more accurate safety exposure calculations and regulatory determinations. Extensive comparisons to in vivo data in humans or closely related animals will be required before accepting flow-through diffusion methods as in vivo alternatives by industry and regulatory bodies. To evaluate the penetration abilities of geraniol and citronellol when they are used in a typical vehicle in consumer products. In vitro skin penetration of radiolabeled geraniol and citronellol was studied under occlusion in human cadaver skin, using flow-through diffusion cells for scintillation counting to determine the percentage of dose absorbed. For comparison, two doses of each material were used: 2% and 5% in 3:1 diethyl phthalate/ethanol. After 24 hours, geraniol and citronellol had relatively low skin absorption rates; 3.8% +/- 2.1% of 2% citronellol, 4.7% +/- 1.9% of 5% citronellol, 3.5% +/- 1.9% of 2% geraniol, and 7.3% +/- 1.1% of 5% geraniol were recovered from skin and receptor fluid compartments. These materials showed good mass-balance recovery. The majority of the dose was recovered in the skin washes (a minimum of 64.7% +/- 4.6% recovered for 2% citronellol and a maximum of 79.3% +/- 3.9% recovered for 5% geraniol). Receptor fluid collection points over time showed a linear

Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

PubMed

Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

2017-08-01

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Occupational dermal exposure to nanoparticles and nano-enabled products: Part I-Factors affecting skin absorption.

PubMed

Larese Filon, Francesca; Bello, Dhimiter; Cherrie, John W; Sleeuwenhoek, Anne; Spaan, Suzanne; Brouwer, Derk H

2016-08-01

The paper reviews and critically assesses the evidence on the relevance of various skin uptake pathways for engineered nanoparticles, nano-objects, their agglomerates and aggregates (NOAA). It focuses especially in occupational settings, in the context of nanotoxicology, risk assessment, occupational medicine, medical/epidemiological surveillance efforts, and the development of relevant exposure assessment strategies. Skin uptake of nanoparticles is presented in the context of local and systemic health effects, especially contact dermatitis, skin barrier integrity, physico-chemical properties of NOAA, and predisposing risk factors, such as stratum corneum disruption due to occupational co-exposure to chemicals, and the presence of occupational skin diseases. Attention should be given to: (1) Metal NOAA, since the potential release of ions may induce local skin effects (e.g. irritation and contact dermatitis) and absorption of toxic or sensitizing metals; (2) NOAA with metal catalytic residue, since potential release of ions may also induce local skin effects and absorption of toxic metals; (3) rigid NOAA smaller than 45nm that can penetrate and permeate the skin; (4) non rigid or flexible NOAA, where due to their flexibility liposomes and micelles can penetrate and permeate the intact skin; (5) impaired skin condition of exposed workers. Furthermore, we outline possible situations where health surveillance could be appropriate where there is NOAA occupational skin exposures, e.g. when working with nanoparticles made of sensitizer metals, NOAA containing sensitizer impurities, and/or in occupations with a high prevalence of disrupted skin barrier integrity. The paper furthermore recommends a stepwise approach to evaluate risk related to NOAA to be applied in occupational exposure and risk assessment, and discusses implications related to health surveillance, labelling, and risk communication. Copyright © 2016 Elsevier GmbH. All rights reserved.

Use of fractional laser microablation and ultrasound to facilitate the delivery of gold nanoparticles into skin in vivo

NASA Astrophysics Data System (ADS)

Terentyuk, G. S.; Genina, Elina A.; Bashkatov, A. N.; Ryzhova, M. V.; Tsyganova, N. A.; Chumakov, D. S.; Khlebtsov, B. N.; Sazonov, A. A.; Dolotov, L. E.; Tuchin, Valerii V.; Khlebtsov, Nikolai G.; Inozemtseva, O. A.

2012-06-01

The delivery of gold nanoparticles (nanocages coated with a layer of silicon dioxide (40/20 nm)) dispersed in the solution (glycerol + polyethylene glycol-400, 1 : 1) into the skin tissue is studied experimentally in vivo. From the data of optical coherence tomography and histochemical analysis it follows that simple application of suspension of nanoparticles is not efficient enough for delivery of the particles into the skin as a result of passive diffusion. It is shown that fractional laser microablation of skin before the application of the suspension, followed by the topical treatment by ultrasound allows penetration through the epidermis layer and delivery of nanoparticles into dermis and hypodermis

Permeation of platinum and rhodium nanoparticles through intact and damaged human skin

NASA Astrophysics Data System (ADS)

Mauro, Marcella; Crosera, Matteo; Bianco, Carlotta; Adami, Gianpiero; Montini, Tiziano; Fornasiero, Paolo; Jaganjac, Morana; Bovenzi, Massimo; Filon, Francesca Larese

2015-06-01

The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na2PtCl6 and RhCl3·3H2O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm-2 h-1 and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin-analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration.

Nuclear microprobe investigation of the penetration of ultrafine zinc oxide into human skin affected by atopic dermatitis

NASA Astrophysics Data System (ADS)

Szikszai, Z.; Kertész, Zs.; Bodnár, E.; Borbíró, I.; Angyal, A.; Csedreki, L.; Furu, E.; Szoboszlai, Z.; Kiss, Á. Z.; Hunyadi, J.

2011-10-01

Skin penetration is one of the potential routes for nanoparticles to gain access into the human body. Ultrafine metal oxides, such as titanium dioxide and zinc oxide are widely used in cosmetic and health products like sunscreens. These oxides are potent UV filters and the particle size smaller than 200 nm makes the product more transparent compared to formulations containing coarser particles. The present study continues the work carried out in the frame of the NANODERM: “Quality of skin as a barrier to ultrafine particles” European project and complements our previous investigations on human skin with compromised barrier function. Atopic dermatitis (a type of eczema) is an inflammatory, chronically relapsing, non-contagious skin disease. It is very common in children but may occur at any age. The exact cause of atopic dermatitis is unknown, but is likely due to a combination of impaired barrier function together with a malfunction in the body's immune system. In this study, skin samples were obtained from two patients suffering from atopic dermatitis. Our results indicate that the ultrafine zinc oxide particles, in a hydrophobic basis gel with an application time of 2 days or 2 weeks, have penetrated deeply into the stratum corneum in these patients. On the other hand, penetration into the stratum spinosum was not observed even in the case of the longer application time.

In vivo skin penetration of macromolecules in irritant contact dermatitis.

PubMed

Abdel-Mottaleb, Mona M A; Lamprecht, Alf

2016-12-30

Recently, a selective preferential accumulation of polymeric nanoparticles (in the size range around 100nm) has been observed in the follicular system of dermatitis skin. The present investigation aimed at clearly investigating the effect of irritant contact dermatitis on the barrier permeability for colloidal systems below this size range, namely quantum dots and hydrophilic macromolecules. Irritant dermatitis was induced in mice and the penetrability of quantum dots (5nm) and hydrophilic dextran molecules has been tracked in both healthy and inflamed skin using confocal laser scanning microscopy. The selective accumulation of the quantum dots was clearly observed in inflamed skin while hydrophilic dextran behaved similarly in both healthy and inflamed skin. The therapeutic potential for the transdermal delivery of peptide drugs through inflamed skin has been also tested in rats. Results revealed that the transdermal permeation of insulin and calcitonin was not significantly enhanced in dermatitis compared to healthy skin. On the other side, permeation through stripped skin was significantly higher. However, the effect was limited and shorter compared to the SC injection where t min was 0.5h and 2h with a 70% and 46% reduction in blood glucose levels for the stripped skin and the SC injection respectively. Similarly, t min was 4h and 8h with area under the curve of 161±65% and 350±97% for the stripped skin and the SC injection respectively. In conclusion, the changes in skin permeability accompanied with skin inflammation did not affect its permeability to peptide drugs. Our findings also underline that experiments with the tape stripped skin model as a surrogate for inflamed skin can risk misleading conclusions due to significant difference of skin permeability between the tape stripped skin and inflamed skin. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo penetration of bare and lipid-coated silica nanoparticles across the human stratum corneum.

PubMed

Iannuccelli, Valentina; Bertelli, Davide; Romagnoli, Marcello; Scalia, Santo; Maretti, Eleonora; Sacchetti, Francesca; Leo, Eliana

2014-10-01

Skin penetration of silica nanoparticles (NP) currently used in pharmaceutical and cosmetic products is a topic of interest not only to evaluate their possible toxicity, but also to understand their behaviour upon contact with the skin and to exploit their potential positive effects in drug or cosmetic delivery field. Therefore, the present work aimed to elucidate the in vivo mechanism by which amorphous hydrophilic silica NP enter human stratum corneum (SC) through the evaluation of the role played by the nanoparticle surface polarity and the human hair follicle density. Two silica samples, bare hydrophilic silica (B-silica, 162±51nm in size) and hydrophobic lipid-coated silica (LC-silica, 363±74nm in size) were applied on both the volar and dorsal side of volunteer forearms. Twelve repetitive stripped tapes were removed from the human skin and evaluated for elemental composition by Energy Dispersive X-ray (EDX) analysis and for silicon content by Inductively Coupled Plasma quadrupole Mass Spectrometry (ICP-MS). All the stripped tapes revealed nanosized structures generally located in the broad spaces between corneocytes and characterized by the same elemental composition (relative weight percentage of silicon and silicon to oxygen weight ratio) than that of the applied samples. However, only about 10% B-silica permeated until the deepest SC layers considered in the study indicating a silica retention in the upper layers of SC, regardless of the hair follicle density. Otherwise, the exposure to LC-silica led to a greater silica skin penetration extent into the deeper SC layers (about 42% and 18% silica following volar and dorsal forearm application, respectively) indicating that the NP surface polarity played a predominant role on that of their size in determining the route and the extent of penetration. Copyright © 2014 Elsevier B.V. All rights reserved.

Penetration of stimuli of fish skin for Acanthostomum brauni cercariae.

PubMed

Ostrowski de Nuñez, M; Haas, W

1991-02-01

The cercaria of Acanthostomum brauni penetrates the skin of its fish host in response to a combination of two chemical signals from the fish skin surface: free fatty acids and a macro-molecular mucus component. The latter seems to be a protein, as the penetration-stimulating activity of fish skin surface mucus is eliminated by digestion with proteinase, but not by digestion with glycosidases, nor by a removal of glycosaminoglycans. These penetration-stimulating host signals differ from the glycoproteins that stimulate the attachment of A. brauni cercariae to the host and also from the macromolecular fish host signals which have been found to stimulate the attachment and penetration by Opisthorchis viverrini cercariae.

Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Leshuai W.; Yu, William W.; Colvin, Vicki L.

2008-04-15

Quantum dots nanoparticles have novel optical properties for biomedical applications and electronics, but little is known about their skin permeability and interaction with cells. QD621 are nail-shaped nanoparticles that contain a cadmium/selenide core with a cadmium sulfide shell coated with polyethylene glycol (PEG) and are soluble in water. QD were topically applied to porcine skin flow-through diffusion cells to assess penetration at 1 {mu}M, 2 {mu}M and 10 {mu}M for 24 h. QD were also studied in human epidermal keratinocytes (HEK) to determine cellular uptake, cytotoxicity and inflammatory potential. Confocal microscopy depicted the penetration of QD621 through the uppermost stratummore » corneum (SC) layers of the epidermis and fluorescence was found primarily in the SC and near hair follicles. QD were found in the intercellular lipid bilayers of the SC by transmission electron microscopy (TEM). Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD both did not detect Cd nor fluorescence signal in the perfusate at any time point or concentration. In HEK, viability decreased significantly (p < 0.05) from 1.25 nM to 10nM after 24 h and 48 h. There was a significant increase in IL-6 at 1.25 nM to 10 nM, while IL-8 increased from 2.5nM to 10nM after 24 h and 48 h. TEM of HEK treated with 10 nM of QD621 at 24 h depicted QD in cytoplasmic vacuoles and at the periphery of the cell membranes. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, yet if the skin were damaged allowing direct QD exposure to skin or keratinocytes, an inflammatory response could be initiated.« less

Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate

PubMed Central

Lopez, Renata F.V.; Seto, Jennifer E.; Blankschtein, Daniel; Langer, Robert

2010-01-01

The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively-coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ~0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500–1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery. PMID:20971504

Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate.

PubMed

Lopez, Renata F V; Seto, Jennifer E; Blankschtein, Daniel; Langer, Robert

2011-01-01

The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ∼0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500-1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery. Copyright © 2010 Elsevier Ltd. All rights reserved.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

PubMed

Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Penetration of Chlorhexidine into Human Skin ▿

PubMed Central

Karpanen, T. J.; Worthington, T.; Conway, B. R.; Hilton, A. C.; Elliott, T. S. J.; Lambert, P. A.

2008-01-01

This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 μm following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 ± 0.047 and 0.077 ± 0.015 μg/mg tissue within the top 100 μm), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 μg/mg tissue below 300 μm). After 24 h of exposure, there was more chlorhexidine within the upper 100-μm sections (7.88 ± 1.37 μg/mg tissue); however, the levels remained low (less than 1 μg/mg tissue) at depths below 300 μm. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice. PMID:18676882

Effect of Size and Surface Charge of Gold Nanoparticles on their Skin Permeability: A Molecular Dynamics Study

PubMed Central

Gupta, Rakesh; Rai, Beena

2017-01-01

Molecular level understanding of permeation of nanoparticles through human skin establishes the basis for development of novel transdermal drug delivery systems and design and formulation of cosmetics. Recent experiments suggest that surface coated nano-sized gold nanoparticles (AuNPs) can penetrate the rat and human skin. However, the mechanisms by which these AuNPs penetrate are not well understood. In this study, we have carried out coarse grained molecular dynamics simulations to explore the permeation of dodecanethiol coated neutral hydrophobic AuNPs of different sizes (2–5 nm) and surface charges (cationic and anionic) through the model skin lipid membrane. The results indicate that the neutral hydrophobic AuNPs disrupted the bilayer and entered in it with in ~200 ns, while charged AuNPs were adsorbed on the bilayer headgroup. The permeation free energy calculation revealed that at the head group of the bilayer, a very small barrier existed for neutral hydrophobic AuNP while a free energy minimum was observed for charged AuNPs. The permeability was maximum for neutral 2 nm gold nanoparticle (AuNP) and minimum for 3 nm cationic AuNP. The obtained results are aligned with recent experimental findings. This study would be helpful in designing customized nanoparticles for cosmetic and transdermal drug delivery application. PMID:28349970

Diverse Host-Seeking Behaviors of Skin-Penetrating Nematodes

PubMed Central

Castelletto, Michelle L.; Gang, Spencer S.; Okubo, Ryo P.; Tselikova, Anastassia A.; Nolan, Thomas J.; Platzer, Edward G.; Lok, James B.; Hallem, Elissa A.

2014-01-01

Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are responsible for some of the most common neglected tropical diseases. The infective larvae of skin-penetrating nematodes are thought to search for hosts using sensory cues, yet their host-seeking behavior is poorly understood. We conducted an in-depth analysis of host seeking in the skin-penetrating human parasite Strongyloides stercoralis, and compared its behavior to that of other parasitic nematodes. We found that Str. stercoralis is highly mobile relative to other parasitic nematodes and uses a cruising strategy for finding hosts. Str. stercoralis shows robust attraction to a diverse array of human skin and sweat odorants, most of which are known mosquito attractants. Olfactory preferences of Str. stercoralis vary across life stages, suggesting a mechanism by which host seeking is limited to infective larvae. A comparison of odor-driven behavior in Str. stercoralis and six other nematode species revealed that parasite olfactory preferences reflect host specificity rather than phylogeny, suggesting an important role for olfaction in host selection. Our results may enable the development of new strategies for combating harmful nematode infections. PMID:25121736

Near infrared laser penetration and absorption in human skin

NASA Astrophysics Data System (ADS)

Nasouri, Babak; Murphy, Thomas E.; Berberoglu, Halil

2014-02-01

For understanding the mechanisms of low level laser/light therapy (LLLT), accurate knowledge of light interaction with tissue is necessary. In this paper, we present a three dimensional, multi-layer Monte Carlo simulation tool for studying light penetration and absorption in human skin. The skin is modeled as a three-layer participating medium, namely epidermis, dermis, and subcutaneous, where its geometrical and optical properties are obtained from the literature. Both refraction and reflection are taken into account at the boundaries according to Snell's law and Fresnel relations. A forward Monte Carlo method was implemented and validated for accurately simulating light penetration and absorption in absorbing and anisotropically scattering media. Local profiles of light penetration and volumetric absorption densities were simulated for uniform as well as Gaussian profile beams with different spreads at 155 mW average power over the spectral range from 1000 nm to 1900 nm. The results show the effects of beam profiles and wavelength on the local fluence within each skin layer. Particularly, the results identify different wavelength bands for targeted deposition of power in different skin layers. Finally, we show that light penetration scales well with the transport optical thickness of skin. We expect that this tool along with the results presented will aid researchers resolve issues related to dose and targeted delivery of energy in tissues for LLLT.

Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle penetration.

PubMed

Priwitaningrum, Dwi L; Blondé, Jean-Baptiste G; Sridhar, Adithya; van Baarlen, Joop; Hennink, Wim E; Storm, Gert; Le Gac, Séverine; Prakash, Jai

2016-12-28

Nanoparticle penetration through tumor tissue after extravasation is considered as a key issue for tumor distribution and therapeutic effects. Most tumors possess abundant stroma, a fibrotic tissue composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which acts as a barrier for nanoparticle penetration. There is however a lack of suitable in vitro systems to study the tumor stroma penetration of nanoparticles. In the present study, we developed and thoroughly characterized a 3D co-culture spheroidal array to mimic tumor stroma and investigated the penetration of silica and PLGA nanoparticles in these spheroids. First, we examined human breast tumor patient biopsies to characterize the content and organization of stroma and found a high expression of alpha-smooth muscle actin (α-SMA; 40% positive area) and collagen-1 (50% positive area). Next, we prepared homospheroids of 4T1 mouse breast cancer cells or 3T3 mouse fibroblasts alone as well as heterospheroids combining 3T3 and 4T1 cells in different ratios (1:1 and 5:1) using a microwell array platform. Confocal live imaging revealed that fibroblasts distributed and reorganized within 48h in heterospheroids. Furthermore, immunohistochemical staining and gene expression analysis showed a proportional increase of α-SMA and collagen in heterospheroids with higher fibroblast ratios attaining 35% and 45% positive area at 5:1 (3T3:4T1) ratio, in a good match with the clinical breast tumor stroma. Subsequently, we studied the penetration of high and low negatively charged fluorescent silica nanoparticles (30nm; red and 100 or 70nm; green; zeta potential: -40mV and -20mV) and as well as Cy5-conjugated pegylated PLGA nanoparticles (200nm, -7mV) in both homo- and heterospheroid models. Fluorescent microscopy on spheroid cryosections after incubation with silica nanoparticles showed that 4T1 homospheroids allowed a high penetration of about 75-80% within 24h, with higher penetration in case of the

Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil.

PubMed

Padois, Karine; Cantiéni, Céline; Bertholle, Valérie; Bardel, Claire; Pirot, Fabrice; Falson, Françoise

2011-09-15

Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex(®) test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

In Vitro Skin Penetration of Petrolatum and Soybean Oil and Effects of Glyceryl Monooleate.

PubMed

Intarakumhaeng, Rattikorn; Shi, Zhanquan; Wanasathop, Apipa; Stella, Q Ching; Wei, Karl S; Styczynski, P B; Li, Chuiying; Smith, Edward D; Li, S Kevin

2018-06-06

Petrolatum and soybean oil are common ingredients incorporated in topical skin formulations for skin protection and moisturization. However, the stratum corneum (SC) penetration kinetics of these two cosmetic ingredients has not been systematically studied. Glyceryl monooleate (GlyMOle) has been shown to enhance skin penetration of various compounds. It was hypothesized that GlyMOle could enhance skin penetration of petrolatum and soybean oil. The present study aimed to examine the in vitro skin penetration of petrolatum and soybean oil in the presence or absence of GlyMOle. Skin permeation experiments were conducted using the in vitro Franz diffusion cell model with split-thickness human skin and human epidermal membrane (HEM). The effect of permeant dose and the kinetics of permeant penetration were examined with and without GlyMOle in vitro. Petrolatum and soybean oil were found to permeate across HEM, and no effect of GlyMOle on skin permeation into the receptor chamber was observed. GlyMOle enhanced the penetration of petrolatum into the split-thickness skin at 50 μg dose (petrolatum:GlyMOle, 49:1, w/w). However, no effect of GlyMOle on petrolatum penetration was observed at 200 μg dose (petrolatum:GlyMOle, 49:1, w/w), indicating a dose-dependent effect. GlyMOle at the level used in the study did not enhance the penetration of soybean oil with 50 and 200 μg doses at any time points. GlyMOle was a skin penetration enhancer for petrolatum under the in vitro conditions identified in the present study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Drug carrier nanoparticles that penetrate human chronic rhinosinusitis mucus

PubMed Central

Lai, Samuel K.; Suk, Jung Soo; Pace, Amanda; Wang, Ying-Ying; Yang, Ming; Mert, Olcay; Chen, Jeane; Kim, Jean; Hanes, Justin

2011-01-01

No effective therapies currently exist for chronic rhinosinusitis (CRS), a persistent inflammatory condition characterized by the accumulation of highly viscoelastic mucus (CRSM) in the sinuses. Nanoparticle therapeutics offer promise for localized therapies for CRS, but must penetrate CRSM in order to avoid washout during sinus cleansing and to reach underlying epithelial cells. Prior research has not established whether nanoparticles can penetrate the tenacious CRSM barrier, or instead become trapped. Here, we first measured the diffusion rates of polystyrene nanoparticles and the same nanoparticles modified with muco-inert polyethylene glycol (PEG) coatings in fresh, minimally perturbed CRSM collected during endoscopic sinus surgery from CRS patients with and without nasal polyp. We found that uncoated polystyrene particles, previously shown to be mucoadhesive, were immobilized in all CRSM samples tested. In contrast, densely PEGylated particles as large as 200 nm were able to readily penetrate all CRSM samples from patients with CRS alone, and nearly half of CRSM samples from patients with nasal polyp. Based on the mobility of different sized PEGylated particles, we estimate the average pore size of fresh CRSM to be at least 150 ± 50 nm. Guided by these studies, we formulated mucus-penetrating particles (MPP) composed of PLGA and Pluronics, two materials with a long history of safety and use in humans. We showed that biodegradable MPP are capable of rapidly penetrating CRSM at average speeds up to only 20-fold slower than their theoretical speeds in water. Our findings strongly support the development of mucus-penetrating nanomedicines for the treatment of CRS. PMID:21665271

Penetration of Ufenamate into Intact, Stripped, or Delipidized Skin Using Different Vehicles.

PubMed

Iino, Hayato; Fujii, Makiko; Fujino, Manami; Koizumi, Naoya; Watanabe, Yoshiteru

2015-01-01

The purpose of this study was to clarify the effect of skin condition on skin penetration of the very high lipophilic drug, ufenamate (UF). UF was applied to stripped or delipidized skin using liquid paraffin (LP) or purified water containing polysorbate 80 at a dose of 2 µL/cm(2). We found that UF penetration into intact and stripped skin using a water vehicle was respectively 5 and 10 times higher than that using LP. UF is freely soluble in oil and insoluble in water; thus, activity in water is higher than that in LP. Therefore, it is useful to use a water-based vehicle for both intact sites and those with defective stratum corneum (SC). Conversely, we found that delipidization of SC decreased the penetration of UF significantly with both LP and water, and the amount measured in the epidermis was 1 µg/cm(2) with both vehicles. This indicates that UF is not suitable for so-called "dry skin." This study revealed clinically relevant differences in the penetration of UF into intact, stripped, or delipidized skin conditions.

Monitoring of copper nanoparticle penetration into dentin of human tooth in vitro

NASA Astrophysics Data System (ADS)

Selifonov, Alexey A.; Glukhovskoy, Evgeny G.; Skibina, Yulia S.; Zakharevich, Andrey M.; Begletsova, Nadezhda N.; Tuchin, Valery V.

2018-04-01

Study of the penetration depth of synthesized copper nanoparticles into cut samples of human dentin was conducted. The scanning electron microscopy was used to determine the elemental composition of fresh transverse cleavage of the dentin cut for determination of the copper nanoparticles penetration with an effective antiseptic effect. The morphology of the cut surface of the dentin of a human tooth was studied and the lower limit of the diffusion boundary was determined. It was found that copper nanoparticles penetrate into the dentin cut to a depth of 1.8 μm with the diffusion coefficient of 1.8×10-11 cm2/s. Despite the rather small size of the synthesized copper nanoparticles (20-80 nm), a rather small penetration depth can be explained by the high aggregation ability of copper nanoparticles, as well as the ability of a micellar solution of sodium dodecyl sulfate, in which nanoparticles were stabilized, to form conglomerates in micelles of much larger sizes.

Simulation of the effect of photoprotective titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles on the thermal response and optical characteristics of skin

NASA Astrophysics Data System (ADS)

Krasnikov, I. V.; Seteikin, A. Yu.; Popov, A. P.

2015-04-01

The thermal response of skin covered with a mixture of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles of optimal sizes and irradiated by sunlight has been calculated. The nanoparticles were rubbed into the skin for maximum protection against the incident radiation. The dependences of the temperature dynamics in different skin layers (corneal layer, epidermis, dermis) have been obtained and analyzed upon skin irradiation with light at a wavelength of 310-800 nm. It has been found that increasing light scattering and absorption due to the nanoparticles introduced into the corneal layer resulted in a decrease in the thermal load and penetration depth of the incident radiation.

Measuring skin penetration by confocal Raman microscopy (CRM): correlation to results from conventional experiments

NASA Astrophysics Data System (ADS)

Lunter, Dominique; Daniels, Rolf

2016-03-01

Confocal Raman microscopy has become an advancing technique in the characterization of drug transport into the skin. In this study the skin penetration of a local anesthetic from a semisolid preparation was investigated. Furthermore, the effect of the chemical enhancers propylene glycol and POE-23-lauryl ether on its penetration was investigated. The results show that confocal Raman microscopy may provide detailed information on the penetration of APIs into the skin and may elucidate their distribution within the skin with high resolution. The results of the CRM analysis are fully in line with those of conventional permeation and penetration experiments.

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

PubMed

Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

2017-01-01

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New CeO2 nanoparticles-based topical formulations for the skin protection against organophosphates.

PubMed

Zenerino, Arnaud; Boutard, Tifenn; Bignon, Cécile; Amigoni, Sonia; Josse, Denis; Devers, Thierry; Guittard, Frédéric

2015-01-01

To reinforce skin protection against organophosphates (OPs), the development of new topical skin protectants (TSP) has received a great interest. Nanoparticles like cerium dioxide (CeO 2 ) known to adsorb and neutralize OPs are interesting candidates for TSP. However, NPs are difficult to disperse into formulations and they are suspected of toxicological issues. Thus, we want to study: (1) the effect of the addition of CeO 2 NPs in formulations for the skin protection (2) the impact of the doping of CeO 2 NPs by calcium; (3) the effect of two methods of dispersion of CeO 2 NPs: an O/W emulsion or a suspension of a fluorinated thickening polymer (HASE-F) grafted with these NPs. As a screening approach we used silicone membranes as a skin equivalent and Franz diffusion cells for permeation tests. The addition of pure CeO 2 NPs in both formulations permits the penetration to decrease by a 3-4-fold factor. The O/W emulsion allows is the best approach to obtain a film-forming coating with a good reproducibility of the penetration results; whereas the grafting of NPs to a thickener is the best way to obtain an efficient homogenous suspension of CeO 2 NPs with a decreased of toxicological impact but the coating is less film-forming which slightly impacts the reproducibility of the penetration results.

Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters.

PubMed

Freitas, J V; Praça, F S G; Bentley, M V L B; Gaspar, L R

2015-04-30

Cutaneous permeation is a critical parameter when topical application of sunscreens containing antioxidants is considered. The aim of this study was to evaluate the cutaneous penetration of most marketed UV-filters combined with trans-resveratrol (RES) and beta-carotene (BTC) since few studies report skin penetration when such compounds are applied. Formulations containing octocrylene, octyl methoxycinnamate, avobenzone and bemotrizinole were prepared and supplemented or not with BTC, or with RES, or with both compounds in combination. Penetration studies were performed using Franz vertical diffusion cells and porcine ear skin as the biological membrane. The quantification of UV-filters and antioxidants in the stratum corneum (SC), viable epidermis plus dermis and receptor fluid was performed by HPLC. Results suggested that UV-filters and antioxidants did not permeate the skin but were retained for 12h post application. About 90% and 80%, respectively, of the total penetrated amount of UV-filters and antioxidants was found in the SC. Interestingly, it was observed that BTC, alone or combined with RES, reduced the skin retention of UV-filters on average by 63%. In conclusion, this study demonstrated that the combination of antioxidants and UV-filters in sunscreens is advantageous for cutaneous penetration, since BTC and BTC+RES improved sunscreen safety by reducing delivery of the four UV-filters in the study into SC and viable epidermis. Copyright © 2015 Elsevier B.V. All rights reserved.

Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study.

PubMed

Badri, Waisudin; Miladi, Karim; Robin, Sophie; Viennet, Céline; Nazari, Qand Agha; Agusti, Géraldine; Fessi, Hatem; Elaissari, Abdelhamid

2017-09-01

This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin. Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used. The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from -19 to -13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well. The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

Scalable Method to Produce Biodegradable Nanoparticles that Rapidly Penetrate Human Mucus

PubMed Central

Xu, Qingguo; Boylan, Nicholas J.; Cai, Shutian; Miao, Bolong; Patel, Himatkumar; Hanes, Justin

2013-01-01

Mucus typically traps and rapidly removes foreign particles from the airways, gastrointestinal tract, nasopharynx, female reproductive tract and the surface of the eye. Nanoparticles capable of rapid penetration through mucus can potentially avoid rapid clearance, and open significant opportunities for controlled drug delivery at mucosal surfaces. Here, we report an industrially scalable emulsification method to produce biodegradable mucus-penetrating particles (MPP). The emulsification of diblock copolymers of poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) using low molecular weight (MW) emulsifiers forms dense brush PEG coatings on nanoparticles that allow rapid nanoparticle penetration through fresh undiluted human mucus. In comparison, conventional high MW emulsifiers, such as polyvinyl alcohol (PVA), interrupts the PEG coating on nanoparticles, resulting in their immobilization in mucus owing to adhesive interactions with mucus mesh elements. PLGA-PEG nanoparticles with a wide range of PEG MW (1, 2, 5, and 10 kDa), prepared by the emulsification method using low MW emulsifiers, all rapidly penetrated mucus. A range of drugs, from hydrophobic small molecules to hydrohilic large biologics, can be efficiently loaded into biodegradable MPP using the method described. This readily scalable method should facilitate the production of MPP products for mucosal drug delivery, as well as potentially longer-circulating particles following intravenous administration. PMID:23751567

Skin penetration operators' knowledge and attitudes towards infection control.

PubMed

Oberdorfer, Aurmporn; Wiggers, John H; Considine, Robyn J; Bowman, Jenny; Cockburn, Jill

2003-01-01

To assess the knowledge and attitudes of owners/managers of commercial skin-penetration premises regarding infection control. A telephone survey was conducted with a randomly selected sample of 874 owners/managers. Participants appeared to lack knowledge of essential infection-control practices. Less than 39% correctly identified recommended disinfection procedures, and between 12% to 67% were not aware of inappropriate sterlization procedures. Almost all participants accepted the need for guidelines. Half acknowledged a need to improve their infection-control compliance, and most accepted having their premises regularly checked by the councils. There is a considerable opportunity to increase infection-control compliance among skin-penetration operators.

Influence of anatomical site and topical formulation on skin penetration of sunscreens

PubMed Central

Benson, Heather AE; Sarveiya, Vikram; Risk, Stacey; Roberts, Michael S

2005-01-01

Sunscreen products are widely used to protect the skin from sun-related damage. Previous studies have shown that some sunscreen chemicals are absorbed across the skin to the systemic circulation. The current study shows that absorption into the skin of sunscreen chemicals applied to the face is up to four times greater than that of the same product applied to the back. This has implications for the way sunscreen products are formulated and may allow the use of less potent products on the face compared with the rest of the body. The effect of formulation vehicles on the release and skin penetration of the common sunscreen agent benzophenone-3 (common name oxybenzone) was also assessed. Penetration of benzophenone-3 across excised human epidermis and high-density polyethylene (HDPE) membrane was measured using in vitro Franz-type diffusion cells. Penetration and epidermal retention was measured following application of infinite and finite (epidermis only) doses of benzophenone-3 in five vehicles: liquid paraffin, coconut oil, 50:50 ethanol:coconut oil, aqueous cream BP, and oily cream BP. Highest benzophenone-3 skin retention was observed for the ethanol:coconut oil combination. Maximal and minimal benzophenone-3 fluxes were observed from liquid paraffin and coconut oil, respectively. The alcohol-based vehicle exhibited low benzophenone-3 release from the vehicle but high skin penetration and retention. PMID:18360561

Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells

PubMed Central

Crosera, Matteo; Prodi, Andrea; Mauro, Marcella; Pelin, Marco; Florio, Chiara; Bellomo, Francesca; Adami, Gianpiero; Apostoli, Pietro; De Palma, Giuseppe; Bovenzi, Massimo; Campanini, Marco; Larese Filon, Francesca

2015-01-01

Titanium dioxide nanoparticles (TiO2NPs) suspensions (concentration 1.0 g/L) in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue® and propidium iodide, PI, uptake assays) was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact and damaged skin. Titanium was found in the epidermal layer after 24 h of exposure (0.47 ± 0.33 μg/cm2) while in the dermal layer, the concentration was below the limit of detection. Damaged skin, in its whole, has shown a similar concentration (0.53 ± 0.26 μg/cm2). Cytotoxicity studies on HaCaT cells demonstrated that TiO2NPs induced cytotoxic effects only at very high concentrations, reducing cell viability after seven days of exposure with EC50s of 8.8 × 10−4 M (MTT assay), 3.8 × 10−5 M (AlamarBlue® assay), and 7.6 × 10−4 M (PI uptake, index of a necrotic cell death). Our study demonstrated that TiO2NPs cannot permeate intact and damaged skin and can be found only in the stratum corneum and epidermis. Moreover, the low cytotoxic effect observed on human HaCaT keratinocytes suggests that these nano-compounds have a potential toxic effect at the skin level only after long-term exposure. PMID:26262634

Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation.

PubMed

Montenegro, Lucia; Sinico, Chiara; Castangia, Ines; Carbone, Claudia; Puglisi, Giovanni

2012-09-15

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30-49 nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers. Copyright © 2012 Elsevier B.V. All rights reserved.

Deep tissue penetration of nanoparticles using pulsed-high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

You, Dong Gil; Yoon, Hong Yeol; Jeon, Sangmin; Um, Wooram; Son, Sejin; Park, Jae Hyung; Kwon, Ick Chan; Kim, Kwangmeyung

2017-11-01

Recently, ultrasound (US)-based drug delivery strategies have received attention to improve enhanced permeation and retention (EPR) effect-based passive targeting efficiency of nanoparticles in vitro and in vivo conditions. Among the US treatment techniques, pulsed-high intensity focused ultrasound (pHIFU) have specialized for improving tissue penetration of various macromolecules and nanoparticles without irreversible tissue damages. In this study, we have demonstrated that pHIFU could be utilized to improve tissue penetration of fluorescent dye-labeled glycol chitosan nanoparticles (FCNPs) in femoral tissue of mice. pHIFU could improve blood flow of the targeted-blood vessel in femoral tissue. In addition, tissue penetration of FCNPs was specifically increased 5.7-, 8- and 9.3-folds than that of non-treated (0 W pHIFU) femoral tissue, when the femoral tissue was treated with 10, 20 and 50 W of pHIFU, respectively. However, tissue penetration of FCNPs was significantly reduced after 3 h post-pHIFU treatment (50 W). Because overdose (50 W) of pHIFU led to irreversible tissue damages, including the edema and chapped red blood cells. These overall results support that pHIFU treatment can enhance the extravasation and tissue penetration of FCNPs as well as induce irreversible tissue damages. We expect that our results can provide advantages to optimize pHIFU-mediated delivery strategy of nanoparticles for further clinical applications.

Modelling skin penetration using the Laplace transform technique.

PubMed

Anissimov, Y G; Watkinson, A

2013-01-01

The Laplace transform is a convenient mathematical tool for solving ordinary and partial differential equations. The application of this technique to problems arising in drug penetration through the skin is reviewed in this paper. © 2013 S. Karger AG, Basel.

Comparison of wavelength-dependent penetration depths of lasers in different types of skin in photodynamic therapy

NASA Astrophysics Data System (ADS)

Mustafa, F. H.; Jaafar, M. S.

2013-03-01

The determination of the penetration depth of laser light with different sources wavelengths into human skin is one of the preconditions of improving the photodynamic therapy (PDT) procedure for skin diseases. This research is planned to explore which wavelengths would be the most advantageous for use in PDT for superficial skin diseases, and to demonstrate that the red laser exposure of 635 nm wavelength is a suitable choice for all skin types in PDT. A realistic skin model (RSM) in the Advanced Systems Analysis Program (ASAP) software has been used to create different types of skin and to simulate laser sources with wavelengths of 635, 532, 405, 365, 308 and 295 nm. The penetration depths of different kinds of laser into the skin as well as their transmission have been calculated. Comparison of the depth of penetration of different wavelengths for all types of skin has been made. A large variation is found in the penetration depth of laser lights in all skin types. The transmission of lasers on the epidermis and dermis in different skin types occur, and the transmission dose changes significantly with the skin depths. The results of the present study provide a basis for understanding the penetration depth of laser in various skin colors and the responses of the skin to laser to improve dose-drug activation in PDT. The differences in spectral transmission between the red laser and the other lasers suggest that the red laser could be a suitable laser for all skin types.

Skin penetration and retention of L-ascorbic acid 2-phosphate using multilamellar vesicles.

PubMed

Yoo, Juno; Shanmugam, Srinivasan; Song, Chung-Kil; Kim, Dae-Duk; Choi, Han-Gon; Yong, Chul-Soon; Woo, Jong-Soo; Yoo, Bong Kyu

2008-12-01

Transdermal formulation of L-ascorbic acid 2-phosphate magnesium salt (A2P) was prepared using multilamellar vesicles (MLV). A2P was either physically mixed with or entrapped into three different MLVs of neutral, cationic, and anionic liposome vesicles. For the preparation of neutral MLVs, phosphatidylcholine (PC) and cholesterol (CH) were used. For cationic and anionic MLVs, dioleoyl-trimethylammonium-propane and dimyristoyl glycerophosphate were added as surface charge inducers, respectively, in addition to PC and CH. Particle size of the three A2P-loaded MLVs was submicron, and polydispersity index revealed homogenous distribution of the prepared MLVs except neutral ones. Skin penetration study with hairless mouse skin showed that both physical mixtures of A2P with empty MLVs and A2P-loaded MLVs increased penetration of the drug compared to aqueous A2P solution. During the penetration, however, significant amount of the drug was metabolized into L-ascorbic acid, which has no beneficial effect on stimulation of hair growth. Out of the physical mixtures and A2P-loaded MLVs tested, physical mixture of A2P with empty cationic MLV resulted in the greatest skin penetration and retention in hairless mouse skin.

31P Solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

PubMed Central

Desai, Pinaki R.; Cormier, Ashley R.; Shah, Punit P.; Patlolla, Ram R.; Paravastu, Anant K.; Singh, Mandip

2013-01-01

The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11 and YKA) through skin intercellular lipids using 31P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, sections (0–60, 61–120 and 121–180 µm) were collected and analyzed for 31P NMR signal. The concentration dependent shift of 0, 25, 50, 100 and 200 mg/ml of TAT on skin layers, diffusion of TAT, R8, R11 and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using 31P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in 31P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180 µm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, 31P solid-state NMR can be used to track CPP penetration into different skin layers. PMID:23702274

Cationic membrane-active peptides - anticancer and antifungal activity as well as penetration into human skin.

PubMed

Do, Nhung; Weindl, Günther; Grohmann, Lisa; Salwiczek, Mario; Koksch, Beate; Korting, Hans Christian; Schäfer-Korting, Monika

2014-05-01

Cationic antimicrobial peptides are ancient natural broad-spectrum antibiotics, and several compounds also exhibit anticancer activity. However, most applications pertain to bacterial infections, and treatment for skin cancer is less frequently considered. The cytotoxicity of melittin, cecropin A, protegrin-1 and histatin 5 against squamous skin cancer cell lines and normal human keratinocytes was evaluated and compared to established drugs. The results show that melittin clearly outperforms 5-fluorouracil regarding antitumor activity. Importantly, combined melittin and 5-fluorouracil enhanced cytotoxic effects on cancer cells and reduced toxicity on normal keratinocytes. Additionally, minimum inhibitory concentrations indicate that melittin also shows superior activity against clinical and laboratory strains of Candida albicans compared to amphotericin B. To evaluate its potential for topical applications, human skin penetration of melittin was investigated ex vivo and compared to two non-toxic cell-penetrating peptides (CPPs), low molecular weight protamine (LMWP) and penetratin. The stratum corneum prevents penetration into viable epidermis over 6 h; however, the peptides gain access to the viable skin after 24 h. Inhibition of digestive enzymes during skin penetration significantly enhances the availability of intact peptide. In conclusion, melittin may represent an innovative agent for non-melanoma skin cancer and infectious skin diseases. In order to develop a drug candidate, skin absorption and proteolytic digestion by skin enzymes need to be addressed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In-vivo dynamic characterization of microneedle skin penetration using optical coherence tomography

NASA Astrophysics Data System (ADS)

Enfield, Joey; O'Connell, Marie-Louise; Lawlor, Kate; Jonathan, Enock; O'Mahony, Conor; Leahy, Martin

2010-07-01

The use of microneedles as a method of circumventing the barrier properties of the stratum corneum is receiving much attention. Although skin disruption technologies and subsequent transdermal diffusion rates are being extensively studied, no accurate data on depth and closure kinetics of microneedle-induced skin pores are available, primarily due to the cumbersome techniques currently required for skin analysis. We report on the first use of optical coherence tomography technology to image microneedle penetration in real time and in vivo. We show that optical coherence tomography (OCT) can be used to painlessly measure stratum corneum and epidermis thickness, as well as microneedle penetration depth after microneedle insertion. Since OCT is a real-time, in-vivo, nondestructive technique, we also analyze skin healing characteristics and present quantitative data on micropore closure rate. Two locations (the volar forearm and dorsal aspect of the fingertip) have been assessed as suitable candidates for microneedle administration. The results illustrate the applicability of OCT analysis as a tool for microneedle-related skin characterization.

Confocal Raman microscopic investigation of the effectiveness of penetration enhancers for procaine delivery to the skin

NASA Astrophysics Data System (ADS)

Lunter, Dominique; Daniels, Rolf

2014-12-01

A methodology that employs confocal Raman microscopy (CRM) on ex vivo skin samples is proposed for the investigation of drug content and distribution in the skin. To this end, the influence of the penetration enhancers propylene glycol and polyoxyethylene-23-lauryl ether on the penetration and permeation of procaine as a model substance was investigated. The drug content of skin samples that had been incubated with semisolid formulations containing one of these enhancers was examined after skin segmentation. The experiments showed that propylene glycol did not affect the procaine content that was delivered to the skin, whereas polyoxyethylene-23-lauryl ether led to higher procaine contents and deeper penetration. Neither substance was found to influence the permeation rate of procaine. It is thereby shown that CRM can provide additional information on drug penetration and permeation. Furthermore, the method was found to enhance the depth from which Raman spectra can be collected and to improve the depth resolution compared to previously proposed methods.

Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance.

PubMed

Strohbehn, Garth; Coman, Daniel; Han, Liang; Ragheb, Ragy R T; Fahmy, Tarek M; Huttner, Anita J; Hyder, Fahmeed; Piepmeier, Joseph M; Saltzman, W Mark; Zhou, Jiangbing

2015-02-01

Current therapy for glioblastoma multiforme (GBM) is largely ineffective, with nearly universal tumor recurrence. The failure of current therapy is primarily due to the lack of approaches for the efficient delivery of therapeutics to diffuse tumors in the brain. In our prior study, we developed brain-penetrating nanoparticles that are capable of penetrating brain tissue and distribute over clinically relevant volumes when administered via convection-enhanced delivery (CED). We demonstrated that these particles are capable of efficient delivery of chemotherapeutics to diffuse tumors in the brain, indicating that they may serve as a groundbreaking approach for the treatment of GBM. In the original study, nanoparticles in the brain were imaged using positron emission tomography (PET). However, clinical translation of this delivery platform can be enabled by engineering a non-invasive detection modality using magnetic resonance imaging (MRI). For this purpose, we developed chemistry to incorporate superparamagnetic iron oxide (SPIO) into the brain-penetrating nanoparticles. We demonstrated that SPIO-loaded nanoparticles, which retain the same morphology as nanoparticles without SPIO, have an excellent transverse (T(2)) relaxivity. After CED, the distribution of nanoparticles in the brain (i.e., in the vicinity of injection site) can be detected using MRI and the long-lasting signal attenuation of SPIO-loaded brain-penetrating nanoparticles lasted over a one-month timecourse. Development of these nanoparticles is significant as, in future clinical applications, co-administration of SPIO-loaded nanoparticles will allow for intraoperative monitoring of particle distribution in the brain to ensure drug-loaded nanoparticles reach tumors as well as for monitoring the therapeutic benefit with time and to evaluate tumor relapse patterns.

Absorption spectra and light penetration depth of normal and pathologically altered human skin

NASA Astrophysics Data System (ADS)

Barun, V. V.; Ivanov, A. P.; Volotovskaya, A. V.; Ulashchik, V. S.

2007-05-01

A three-layered skin model (stratum corneum, epidermis, and dermis) and engineering formulas for radiative transfer theory are used to study absorption spectra and light penetration depths of normal and pathologically altered skin. The formulas include small-angle and asymptotic approximations and a layer-addition method. These characteristics are calculated for wavelengths used for low-intensity laser therapy. We examined several pathologies such as vitiligo, edema, erythematosus lupus, and subcutaneous wound, for which the bulk concentrations of melanin and blood vessels or tissue structure (for subcutaneous wound) change compared with normal skin. The penetration depth spectrum is very similar to the inverted blood absorption spectrum. In other words, the depth is minimal at blood absorption maxima. The calculated absorption spectra enable the power and irradiation wavelength providing the required light effect to be selected. Relationships between the penetration depth and the diffuse reflectance coefficient of skin (unambiguously expressed through the absorption coefficient) are analyzed at different wavelengths. This makes it possible to find relationships between the light fields inside and outside the tissue.

Transdermal delivery of biomacromolecules using lipid-like nanoparticles

NASA Astrophysics Data System (ADS)

Bello, Evelyn A.

The transdermal delivery of biomacromolecules, including proteins and nucleic acids, is challenging, owing to their large size and the penetration-resistant nature of the stratum corneum. Thus, an urgent need exists for the development of transdermal delivery methodologies. This research focuses on the use of cationic lipid-like nanoparticles (lipidoids) for the transdermal delivery of proteins, and establishes an in vitro model for the study. The lipidoids used were first combinatorially designed and synthesized; afterwards, they were employed for protein encapsulation in a vesicular system. A skin penetration study demonstrated that lipidoids enhance penetration depth in a pig skin model, overcoming the barrier that the stratum corneum presents. This research has successfully identified active lipidoids capable of efficiently penetrating the skin; therefore, loading proteins into lipidoid nanoparticles will facilitate the transdermal delivery of proteins. Membrane diffusion experiments were used to confirm the results. This research has confirmed that lipidoids are a suitable material for transdermal protein delivery enhancement.

Stimulation of the penetration of particles into the skin by plasma tissue interaction

NASA Astrophysics Data System (ADS)

Lademann, O.; Richter, H.; Kramer, A.; Patzelt, A.; Meinke, M. C.; Graf, C.; Gao, Q.; Korotianskiy, E.; Rühl, E.; Weltmann, K.-D.; Lademann, J.; Koch, S.

2011-10-01

A high number of treatments in dermatology are based on the penetration of topically applied drugs through the skin barrier. This process is predominantly inefficient, on account of the strong protection properties of the upper skin layer - the stratum corneum. If the skin barrier is damaged, the penetration efficiency of topically applied drugs increases. Therefore, different methods have been developed to influence the barrier properties of the skin. Recently, it could be demonstrated that a cold tissue tolerable plasma (TTP) produced by a plasma-jet can strongly enhance drug delivery through the skin. These investigations were performed by using a solution of fluorescent dye as a model drug. In the present study, these investigations were carried out using fluorescent silica particles at different sizes. The aim of the study was to investigate whether or not there is a limitation in size for topically applied substances to pass through the skin barrier after plasma treatment.

Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen.

PubMed

Abd, Eman; Namjoshi, Sarika; Mohammed, Yousuf H; Roberts, Michael S; Grice, Jeffrey E

2016-01-01

We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity.

Effect of solute lipophilicity on penetration through canine skin.

PubMed

Mills, P C; Magnusson, B M; Cross, S E

2003-12-01

To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin. Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radiolabelled (14C) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19-3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (kP, cm/h), maximum flux (Jmax, mol/cm2/h) and residue remaining within the skin were determined. The kP increased with increasing lipophilicity (6.2 x 10(-4) +/- 1.6 x 10(-4) cm/h for ethanol to 1.8 x 10(-2) +/- 3.6 x 10(-3) cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin.

Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases

PubMed Central

Zhang, Zheng; Tsai, Pei-Chin; Ramezanli, Tannaz; Michniak-Kohn, Bozena B.

2013-01-01

Human skin not only functions as a permeation barrier (mainly due to the stratum corneum layer), but also provides a unique delivery pathway for therapeutic and other active agents. These compounds penetrate via intercellular, intracellular and transappendageal routes, resulting in topical delivery (into skin strata) and transdermal delivery (to subcutaneous tissues and into the systemic circulation). Passive and active permeation enhancement methods have been widely applied to increase the cutaneous penetration. The pathology, pathogenesis and topical treatment approaches of dermatological diseases, such as psoriasis, contact dermatitis, and skin cancer, are then discussed. Recent literature has demonstrated that nanoparticles-based topical delivery systems can be successful in treating these skin conditions. The studies are reviewed starting with the nanoparticles based on natural polymers specially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters) and non-degradable (polyarylates) polymers; emphasis is given to nanospheres made of polymers derived from naturally occurring metabolites, the tyrosine-derived nanospheres (TyroSpheres™). In summary, the nanoparticles-based topical delivery systems combine the advantages of both the nano-sized drug carriers and the topical approach, and are promising for the treatment of skin diseases. For the perspectives, the penetration of ultra-small nanoparticles (size smaller than 40 nm) into skin strata, the targeted delivery of the encapsulated drugs to hair follicle stem cells, and the combination of nanoparticles and microneedle array technologies for special applications such as vaccine delivery are discussed. PMID:23386536

The effect of mangiferin on skin: Penetration, permeation and inhibition of ECM enzymes.

PubMed

Ochocka, Renata; Hering, Anna; Stefanowicz-Hajduk, Justyna; Cal, Krzysztof; Barańska, Helena

2017-01-01

Mangiferin (2-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a polyphenol with strong antioxidant properties. Mangiferin is obtained from the mango tree (Mangifera indica L., Anacardiaceae). It has been proven that mangiferin exhibits many pharmacological activities. The aim of this study was to analyze the penetration of mangiferin into the human skin and through the skin. According to our knowledge, skin penetration and permeation studies of mangiferin have not been analyzed so far. Additionally, the influence of mangiferin on two Extracellular Matrix Enzymes (ECM): collagenase and elastase, was evaluated for the first time. It has been indicated that mangiferin is able to permeate the stratum corneum and penetrate into the epidermis and dermis in comparable amounts. For confirmation of the obtained results, fluorescence microscopy was successfully utilized. The analysis revealed the capability of mangiferin to reversibly inhibit elastase and collagenase activity. The mechanism of mangiferin interaction with both enzymes was estimated as a noncompetitive inhibition.

The effect of mangiferin on skin: Penetration, permeation and inhibition of ECM enzymes

PubMed Central

Hering, Anna; Stefanowicz–Hajduk, Justyna; Cal, Krzysztof; Barańska, Helena

2017-01-01

Mangiferin (2-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a polyphenol with strong antioxidant properties. Mangiferin is obtained from the mango tree (Mangifera indica L., Anacardiaceae). It has been proven that mangiferin exhibits many pharmacological activities. The aim of this study was to analyze the penetration of mangiferin into the human skin and through the skin. According to our knowledge, skin penetration and permeation studies of mangiferin have not been analyzed so far. Additionally, the influence of mangiferin on two Extracellular Matrix Enzymes (ECM): collagenase and elastase, was evaluated for the first time. It has been indicated that mangiferin is able to permeate the stratum corneum and penetrate into the epidermis and dermis in comparable amounts. For confirmation of the obtained results, fluorescence microscopy was successfully utilized. The analysis revealed the capability of mangiferin to reversibly inhibit elastase and collagenase activity. The mechanism of mangiferin interaction with both enzymes was estimated as a noncompetitive inhibition. PMID:28750062

Light-Emitting Photon-Upconversion Nanoparticles in the Generation of Transdermal Reactive-Oxygen Species.

PubMed

Prieto, Martin; Rwei, Alina Y; Alejo, Teresa; Wei, Tuo; Lopez-Franco, Maria Teresa; Mendoza, Gracia; Sebastian, Victor; Kohane, Daniel S; Arruebo, Manuel

2017-12-06

Common photosensitizers used in photodynamic therapy do not penetrate the skin effectively. In addition, the visible blue and red lights used to excite such photosensitizers have shallow penetration depths through tissue. To overcome these limitations, we have synthesized ultraviolet- and visible-light-emitting, energy-transfer-based upconversion nanoparticles and coencapsulated them inside PLGA-PEG (methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid)) nanoparticles with the photosensitizer protoporphyrin IX. Nd 3+ has been introduced as a sensitizer in the upconversion nanostructure to allow its excitation at 808 nm. The subcytotoxic doses of the hybrid nanoparticles have been evaluated on different cell lines (i.e., fibroblasts, HaCaT, THP-1 monocytic cell line, U251MG (glioblastoma cell line), and mMSCs (murine mesenchymal stem cells). Upon NIR (near infrared)-light excitation, the upconversion nanoparticles emitted UV and VIS light, which consequently activated the generation of reactive-oxygen species (ROS). In addition, after irradiating at 808 nm, the resulting hybrid nanoparticles containing both upconversion nanoparticles and protoporphyrin IX generated 3.4 times more ROS than PLGA-PEG nanoparticles containing just the same dose of protoporphyrin IX. Their photodynamic effect was also assayed on different cell cultures, demonstrating their efficacy in selectively killing treated and irradiated cells. Compared to the topical application of the free photosensitizer, enhanced skin permeation and penetration were observed for the nanoparticulate formulation, using an ex vivo human-skin-permeation experiment. Whereas free protoporphyrin IX remained located at the outer layer of the skin, nanoparticle-encapsulated protoporphyrin IX was able to penetrate through the epidermal layer slightly into the dermis.

Topical application of nanoparticles: prospects and safety aspects (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lademann, Jürgen M.; Richter, Heike; Jung, Sora; Meinke, Martina C.; Rühl, Eckart; Alexiev, Ulrike; Calderon, Marcelo; Patzelt, Alexa

2016-03-01

The requirements on nanoparticles for cosmetic and medical applications are very different. While nanoparticles applied in sunscreens shall remain on the skin surface or in the upper cell layers of the stratum corneum, nanoparticles for medical drug delivery shall penetrate through the skin barrier to the target structures in the living cells. Under the Collaborative Research Project 1112 various methods are used at the CCP to investigate the cutaneous penetration and storage of nanoparticles, hair follicles being in the focus of attention. Human hair follicles are ideal target structures for drug delivery. Hosting both the stem and dendritic cells, they are surrounded by a dense network of blood vessels. Investigating nanoparticles of different size and materials, particles of approximately 600 nm in diameter were found to penetrate best into the hair follicles, where they can be stored for maximally 10 days. Their retention time in the hair follicles exceeds that in the stratum corneum by almost one order of magnitude. Particles penetrate more efficiently into the hair follicles than non-particulate substances. For particles from 40 nm-1 µm in diameter, however, no follicular penetration has been detectable if the skin barrier was intact. This is plausible as the hair follicle has its own barrier. It will be demonstrated that the best way for drug delivery is the application of drug-loaded particulate carrier systems. In the hair follicles the particles may either dissolve and release the drug, or an external signal must trigger the drug release from the particle.

Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies.

PubMed

Wilkinson, Simon C; Maas, Wilfred J M; Nielsen, Jesper Bo; Greaves, Laura C; van de Sandt, Johannes J M; Williams, Faith M

2006-05-01

To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56-1.36 mm). A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

PubMed Central

Tang, Benjamin C.; Dawson, Michelle; Lai, Samuel K.; Wang, Ying-Ying; Suk, Jung Soo; Yang, Ming; Zeitlin, Pamela; Boyle, Michael P.; Fu, Jie; Hanes, Justin

2009-01-01

Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lactic-co-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces. PMID:19901335

Time-resolved fluorescence microscopy (FLIM) as an analytical tool in skin nanomedicine.

PubMed

Alexiev, Ulrike; Volz, Pierre; Boreham, Alexander; Brodwolf, Robert

2017-07-01

The emerging field of nanomedicine provides new approaches for the diagnosis and treatment of diseases, for symptom relief, and for monitoring of disease progression. Topical application of drug-loaded nanoparticles for the treatment of skin disorders is a promising strategy to overcome the stratum corneum, the upper layer of the skin, which represents an effective physical and biochemical barrier. The understanding of drug penetration into skin and enhanced penetration into skin facilitated by nanocarriers requires analytical tools that ideally allow to visualize the skin, its morphology, the drug carriers, drugs, their transport across the skin and possible interactions, as well as effects of the nanocarriers within the different skin layers. Here, we review some recent developments in the field of fluorescence microscopy, namely Fluorescence Lifetime Imaging Microscopy (FLIM)), for improved characterization of nanocarriers, their interactions and penetration into skin. In particular, FLIM allows for the discrimination of target molecules, e.g. fluorescently tagged nanocarriers, against the autofluorescent tissue background and, due to the environmental sensitivity of the fluorescence lifetime, also offers insights into the local environment of the nanoparticle and its interactions with other biomolecules. Thus, FLIM shows the potential to overcome several limits of intensity based microscopy. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced chlorhexidine skin penetration with 1,8-cineole.

PubMed

Casey, A L; Karpanen, T J; Conway, B R; Worthington, T; Nightingale, P; Waters, R; Elliott, T S J

2017-05-17

Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 μm slices to a depth of 2000 μm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection.

Comparison of penetration and metabolism of [3H]diacetoxyscirpenol, [3H]verrucarin A and [3H]T-2 toxin in skin.

PubMed

Kemppainen, B W; Riley, R T; Biles-Thurlow, S

1987-05-01

The purpose of this research was to determine the rate of cutaneous penetration and metabolism of [3H]diacetoxyscirpenol (DAS) and [3H]verrucarin A (VCA) and compare these values to previously determined values for [3H]T-2 toxin (T-2), to compare the cutaneous penetration and metabolism of DAS in human and guinea-pig skin, and to compare the effects of dose and of two vehicles, methanol and dimethylsulphoxide (DMSO), on penetration rates. DAS or VCA was applied to the epidermal surface of excised skin, and the receptor fluid bathing the dermal surface was sampled periodically for 48 hr. Whether the applied dose (581 ng/cm2) was dissolved in methanol or DMSO, the rate of penetration through human skin was lower for VCA than for DAS or T-2, the rates for the two latter compounds being similar at this dose. Metabolism of DAS occurred during penetration through excised human skin and did not occur in the receptor fluid as a result of enzymes leaching out of the skin. VCA appeared to be metabolized by human skin, but this conclusion is tentative because of the relative instability of this compound. DAS penetrated significantly (P less than 0.05) faster through excised guinea-pig skin than through human skin. Metabolism of DAS was greater in human skin than in guinea-pig skin. When compared with methanol, DMSO increased the penetration of DAS and VCA by factors of between 7 and 52. At the low dose (79 ng/cm2) DAS penetrated human and guinea-pig skin significantly (P less than 0.05) faster than T-2 using either vehicle.

Measuring the penetration of a skin sensitizer and its delivery vehicles simultaneously with confocal Raman spectroscopy.

PubMed

Bonnist, E Y M; Gorce, J-P; Mackay, C; Pendlington, R U; Pudney, P D A

2011-01-01

Among the factors determining the propensity of a chemical to induce skin allergy are the penetration into skin and the kinetics of ingress. Confocal Raman spectroscopy can provide such information as it enables direct, spatially resolved measurement of the skin and of any chemical uptake. Several chemicals can be monitored at once, and the method is non-destructive (light in, light out) so that the skin can be kept intact for repeated and continuous measurement. Raman spectroscopy was used to follow the penetration of 2.5 weight percent trans-cinnamaldehyde and its delivery vehicle into skin in vitro, up to 24 h after topical application. A custom-made Bronaugh-type diffusion cell that was suitable for the Raman experiment was used. Four different vehicles were tested: absolute ethanol, 50% aqueous ethanol, propylene glycol and acetone:olive oil (4:1); these gave different time scales for cinnamaldehyde penetration. The acetone:olive oil vehicle phase-separated on the skin surface and the cinnamaldehyde penetrated at different rates in the different phases, which may be of significance since this is the preferred solvent for the local lymph node assay (an in vivo animal test used to generate hazard information on skin sensitization). In conclusion, the Raman method gives valuable detailed information on chemical ingress, clearly differentiates between different delivery rates and allows solvent monitoring alongside the chemical of interest. Copyright © 2011 S. Karger AG, Basel.

Effect of different penetration enhancers on diclofenac permeation across horse skin.

PubMed

Ferrante, M; Andreeta, A; Landoni, M F

2010-12-01

Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug widely used in humans and animals. Previous reports have shown that this compound has low percutaneous absorption in horses. The effect of five penetration enhancers (10% urea, 15% and 20% oleic acid and 5% and 10% d-limonene) on the percutaneous absorption of diclofenac diethylamine through horse skin was evaluated in vitro using Franz-type diffusion cells. All tested penetration enhancers induced a significant increase in diclofenac diethylamine permeation, with limonene showing the highest enhancing effect at the lowest concentration (5%) applied. The presence of the permeation enhancers did not affect lag-time. This is the first in vitro study of the effects of penetration enhancers on transdermal permeation of diclofenac diethylamine across horse skin. The results suggested that urea, limonene and 5% oleic acid were useful for enhancing the transdermal absorption of diclofenac diethylamine and may assist in the development of a transdermal formulation of diclofenac diethylamine for use in horses. Copyright © 2009. Published by Elsevier Ltd.

A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system

NASA Astrophysics Data System (ADS)

Chen, Huabing; Xiao, Ling; Du, Danrong; Mou, Dongsheng; Xu, Huibi; Yang, Xiangliang

2010-01-01

We report a novel facile method for preparing stable nanoparticles with inner spherical solid spheres and an outer hydrogel matrix using a hot O/W hydrogel-thickened microemulsion with spontaneous stability. The nanoparticles with average diameters of about 30.0 nm and 100.0 nm were constructed by cooling the hot hydrogel-thickened microemulsion at different temperatures, respectively. We explained the application of these nanoparticles by actualizing the cutaneous delivery of drug-loaded nanoparticles. The in vitro skin permeation studies showed that the nanoparticles could significantly reduce the penetration of model drugs through skin and resulted in their dermal uptakes in skin. The sol-gel process of TEOS was furthermore used in the template of HTM to regulate the particle size of nanoparticles. The coating of silica on the surface of nanoparticles could regulate the penetration of drug into skin from dermal delivery to transdermal delivery. This strategy provides a facile method to produce nanoparticles with long-term stability and ease of manufacture, which might have a promising application in drug delivery.

The hyperelastic and failure behaviors of skin in relation to the dynamic application of microscopic penetrators in a murine model.

PubMed

Meliga, Stefano C; Coffey, Jacob W; Crichton, Michael L; Flaim, Christopher; Veidt, Martin; Kendall, Mark A F

2017-01-15

In-depth understanding of skin elastic and rupture behavior is fundamental to enable next-generation biomedical devices to directly access areas rich in cells and biomolecules. However, the paucity of skin mechanical characterization and lack of established fracture models limits their rational design. We present an experimental and numerical study of skin mechanics during dynamic interaction with individual and arrays of micro-penetrators. Initially, micro-indentation of individual skin strata revealed hyperelastic moduli were dramatically rate-dependent, enabling extrapolation of stiffness properties at high velocity regimes (>1ms -1 ). A layered finite-element model satisfactorily predicted the penetration of micro-penetrators using characteristic fracture energies (∼10pJμm -2 ) significantly lower than previously reported (≫100pJμm -2 ). Interestingly, with our standard application conditions (∼2ms -1 , 35gpistonmass), ∼95% of the application kinetic energy was transferred to the backing support rather than the skin ∼5% (murine ear model). At higher velocities (∼10ms -1 ) strain energy accumulated in the top skin layers, initiating fracture before stress waves transmitted deformation to the backing material, increasing energy transfer efficiency to 55%. Thus, the tools developed provide guidelines to rationally engineer skin penetrators to increase depth targeting consistency and payload delivery across patients whilst minimizing penetration energy to control skin inflammation, tolerability and acceptability. The mechanics of skin penetration by dynamically-applied microscopic tips is investigated using a combined experimental-computational approach. A FE model of skin is parameterized using indentation tests and a ductile-failure implementation validated against penetration assays. The simulations shed light on skin elastic and fracture properties, and elucidate the interaction with microprojection arrays for vaccine delivery allowing rational

Drug delivery with topically applied nanoparticles: science fiction or reality.

PubMed

Lademann, J; Richter, H; Meinke, M C; Lange-Asschenfeldt, B; Antoniou, C; Mak, W C; Renneberg, R; Sterry, W; Patzelt, A

2013-01-01

The efficacy of topically applied drugs is determined by their action mechanism and their potential capacity of passing the skin barrier. Nanoparticles are assumed to be efficient carrier systems for drug delivery through the skin barrier. For flexible nanoparticles like liposomes, this effect has been well demonstrated. The penetration properties of solid nanoparticles are currently under intensive investigation. The crucial advantage of nanoparticles over non-particulate substances is their capability to penetrate deeply into the hair follicles where they can be stored for several days. There is no evidence, yet, that solid particles ≥40 nm are capable of passing through the healthy skin barrier. Therefore and in spite of the long-standing research efforts in this field, commercially available solid nanoparticle-based products for drug delivery through the healthy skin are still missing. Nevertheless, the prospects for the clinical use of nanoparticles in drug delivery are tremendous. They can be designed as transport systems delivering drugs efficiently into the hair follicles in the vicinity of specific target structures. Once deposited at these structures, specific signals might trigger the release of the drugs and exert their effects on the target cells. In this article, examples of such triggered drug release are presented. © 2013 S. Karger AG, Basel.

Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity

PubMed Central

Mauro, Marcella; Crosera, Matteo; Pelin, Marco; Florio, Chiara; Bellomo, Francesca; Adami, Gianpiero; Apostoli, Piero; De Palma, Giuseppe; Bovenzi, Massimo; Campanini, Marco; Larese Filon, Francesca

2015-01-01

Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs) have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1) and needle-abraded human skin (experiment 2). Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2), while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2) and those with intact skin (1.08 ± 0.20 ng·cm−2). To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI) uptake assays. The results indicate that a long exposure time (i.e., seven days) was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay; 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay) that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay). This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure. PMID:26193294

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

PubMed Central

Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

2014-01-01

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around −30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies.

PubMed

Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

2014-01-01

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics

Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal delivery: cancer therapy by circumventing the skin barrier.

PubMed

Rao, Yue-feng; Chen, Wei; Liang, Xing-guang; Huang, Yong-zhuo; Miao, Jing; Liu, Lin; Lou, Yan; Zhang, Xing-guo; Wang, Ben; Tang, Rui-kang; Chen, Zhong; Lu, Xiao-yang

2015-01-14

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancement of Skin Penetration of Hydrophilic and Lipophilic Compounds by pH-sensitive Liposomes.

PubMed

Tokudome, Yoshihiro; Nakamura, Kaoru; Itaya, Yurina; Hashimoto, Fumie

2015-01-01

Enhance skin penetration of hydrophilic and lipophilic compounds using liposomes that are responsible to the pH of the skin surface. pH-sensitive liposomes were prepared by a thin layer and freeze-thaw method with dioleoyl phosphatidyl ethanolamine and cholesteryl hemisuccinate. Liposomal fusion with stratum corneum lipid liposomes was measured using fluorescence resonance energy transfer. Particle diameter and zeta potential of the liposomes after fusion were measured by dynamic light scattering and electrophoresis. Under neutral pH conditions, the diameter of the pH-sensitive liposomes was 130 nm and their zeta potential was -70 mV. In weakly acidic conditions, the diameter was larger than 3,000 nm and the zeta potential was -50 mV. In contrast, the particle diameter and the zeta potential of the non-pH-sensitive liposomes remained constant under various pH conditions. A skin penetration study was performed on hairless mice skin using vertical diffusion cells, showing that the fusion ability of pH-sensitive liposomes was higher than that of non-pH-sensitive liposomes. In the skin penetration study was carried out using hydrophilic (calcein) and lipophilic (N-(7-nitrobenz- 2-oxa-1,3-diazol-4yl)-PE) (NBD-PE) model compounds which were applied to the skin with pH-sensitive liposomes as carrier. The fluorescent compounds contained within the pH-sensitive liposomes permeated the skin more effectively than those within non-pH-sensitive liposomes, and this ability was further enhanced with the lipophilic compound. These studies suggest that pH-sensitive liposomes have potential as an important tool for delivery of compounds into the skin.

Nanoparticle penetration and transport in living pumpkin plants: in situ subcellular identification

PubMed Central

Corredor, Eduardo; Testillano, Pilar S; Coronado, María-José; González-Melendi, Pablo; Fernández-Pacheco, Rodrigo; Marquina, Clara; Ibarra, M Ricardo; de la Fuente, Jesús M; Rubiales, Diego; Pérez-de-Luque, Alejandro; Risueño, María-Carmen

2009-01-01

Background In recent years, the application of nanotechnology in several fields of bioscience and biomedicine has been studied. The use of nanoparticles for the targeted delivery of substances has been given special attention and is of particular interest in the treatment of plant diseases. In this work both the penetration and the movement of iron-carbon nanoparticles in plant cells have been analyzed in living plants of Cucurbita pepo. Results The nanoparticles were applied in planta using two different application methods, injection and spraying, and magnets were used to retain the particles in movement in specific areas of the plant. The main experimental approach, using correlative light and electron microscopy provided evidence of intracellular localization of nanoparticles and their displacement from the application point. Long range movement of the particles through the plant body was also detected, particles having been found near the magnets used to immobilize and concentrate them. Furthermore, cell response to the nanoparticle presence was detected. Conclusion Nanoparticles were capable of penetrating living plant tissues and migrating to different regions of the plant, although movements over short distances seemed to be favoured. These findings show that the use of carbon coated magnetic particles for directed delivery of substances into plant cells is a feasible application. PMID:19389253

Towards understanding the mechanisms and the kinetics of nanoparticle penetration through protective gloves

NASA Astrophysics Data System (ADS)

Vinches, L.; Peyrot, C.; Lemarchand, L.; Boutrigue, N.; Zemzem, M.; Wilkinson, K. J.; Hallé, S.; Tufenkji, N.

2015-05-01

Parallel to the increased use of engineered nanoparticles (ENP) in the formulation of commercial products or in medicine, numerous health & safety agencies have recommended the application of the precautionary principle to handle ENP; namely, the recommendation to use protective gloves against chemicals. However, recent studies reveal the penetration of titanium dioxide nanoparticles through nitrile rubber protective gloves in conditions simulating occupational use. This project is designed to understand the links between the penetration of gold nanoparticles (nAu) through nitrile rubber protective gloves and the mechanical and physical behaviour of the elastomer material subjected to conditions simulating occupational use (i.e., mechanical deformations (MD) and sweat). Preliminary analyses show that nAu suspensions penetrate selected glove materials after exposure to prolonged (3 hours) dynamic deformations. Significant morphological changes are observed on the outer surface of the glove sample; namely, the number and the surface of the micropores on the surface increase. Moreover, nitrile rubber protective gloves are also shown to be sensitive to the action of nAu suspension and to the action of the saline solution used to simulate sweat (swelling).

Non-Darcian flow to a partially penetrating well in a confined aquifer with a finite-thickness skin

NASA Astrophysics Data System (ADS)

Feng, Qinggao; Wen, Zhang

2016-08-01

Non-Darcian flow to a partially penetrating well in a confined aquifer with a finite-thickness skin was investigated. The Izbash equation is used to describe the non-Darcian flow in the horizontal direction, and the vertical flow is described as Darcian. The solution for the newly developed non-Darcian flow model can be obtained by applying the linearization procedure in conjunction with the Laplace transform and the finite Fourier cosine transform. The flow model combines the effects of the non-Darcian flow, partial penetration of the well, and the finite thickness of the well skin. The results show that the depression cone spread is larger for the Darcian flow than for the non-Darcian flow. The drawdowns within the skin zone for a fully penetrating well are smaller than those for the partially penetrating well. The skin type and skin thickness have great impact on the drawdown in the skin zone, while they have little influence on drawdown in the formation zone. The sensitivity analysis indicates that the drawdown in the formation zone is sensitive to the power index ( n), the length of well screen ( w), the apparent radial hydraulic conductivity of the formation zone ( K r2), and the specific storage of the formation zone ( S s2) at early times, and it is very sensitive to the parameters n, w and K r2 at late times, especially to n, while it is not sensitive to the skin thickness ( r s).

Laser Scanning Microscopic Investigations of the Decontamination of Soot Nanoparticles from the Skin.

PubMed

Lademann, Jürgen; Knorr, Fanny; Patzelt, Alexa; Meinke, Martina C; Richter, Heike; Krutmann, Jean; Rühl, Eckart; Doucet, Olivier

2018-01-01

Airborne pollutants, such as nano-sized soot particles, are increasingly being released into the environment as a result of growing population densities and industrialization. They can absorb organic and metal compounds with potential biological activity, such as polycyclic aromatic hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be induced in the skin if the particulates release their harmful components upon dermal contact. In the present study, skin pretreatments with serum and/or shield as barrier formulations prior to exposure and washing with a cleanser subsequent to exposure were evaluated as a protection and decontamination strategy using laser scanning microscopy. The results indicate that while the application of serum and a cleanser was insufficient for decontamination, the pretreatment with shield prior to nanoparticle exposure followed by washing led to the removal of a considerable amount of the carbon black particles. The combined application of serum and shield before the administration of carbon black particles and subsequent washing led to their elimination from the skin samples. The application of barrier-enhancing formulations in combination with a cleanser may reduce the penetration of harmful airborne particulates by preventing their adhesion to the skin and facilitating their removal by subsequent washing with the cleanser. © 2018 S. Karger AG, Basel.

Palladium nanoparticles exposure: Evaluation of permeation through damaged and intact human skin.

PubMed

Larese Filon, Francesca; Crosera, Matteo; Mauro, Marcella; Baracchini, Elena; Bovenzi, Massimo; Montini, Tiziano; Fornasiero, Paolo; Adami, Gianpiero

2016-07-01

The intensified use of palladium nanoparticles (PdNPs) in many chemical reactions, jewellery, electronic devices, in car catalytic converters and in biomedical applications lead to a significant increase in palladium exposure. Pd can cause allergic contact dermatitis when in contact with the skin. However, there is still a lack of toxicological data related to nano-structured palladium and information on human cutaneous absorption. In fact, PdNPs, can be absorbed through the skin in higher amounts than bulk Pd because NPs can release more ions. In our study, we evaluated the absorption of PdNPs, with a size of 10.7 ± 2.8 nm, using intact and damaged human skin in Franz cells. 0.60 mg cm(-2) of PdNPs were applied on skin surface for 24 h. Pd concentrations in the receiving solutions at the end of experiments were 0.098 ± 0.067 μg cm(-2) and 1.06 ± 0.44 μg cm(-2) in intact skin and damaged skin, respectively. Pd flux permeation after 24 h was 0.005 ± 0.003 μg cm(-2) h(-1) and 0.057 ± 0.030 μg cm(-2) h(-1) and lag time 4.8 ± 1.7 and 4.2 ± 3.6 h, for intact and damaged skin respectively. This study indicates that Pd can penetrate human skin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

PubMed Central

Kumar, Amit; Li, Xinran; Sandoval, Michael A; Rodriguez, B Leticia; Sloat, Brian R; Cui, Zhengrong

2011-01-01

Background: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection. Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection. Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection. PMID:21753877

Skin penetration and kinetics of pristine fullerenes (C{sub 60}) topically exposed in industrial organic solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Xin R., E-mail: xia@ncsu.ed; Monteiro-Riviere, Nancy A.; Riviere, Jim E.

2010-01-01

Pristine fullerenes (C{sub 60}) in different solvents will be used in many industrial and pharmaceutical manufacturing and derivatizing processes. This report explores the impact of solvents on skin penetration of C{sub 60} from different types of industrial solvents (toluene, cyclohexane, chloroform and mineral oil). Yorkshire weanling pigs (n = 3) were topically dosed with 500 muL of 200 mug/mL C{sub 60} in a given solvent for 24 h and re-dosed daily for 4 days to simulate the worst scenario in occupational exposures. The dose sites were tape-stripped and skin biopsies were taken after 26 tape-strips for quantitative analysis. When dosedmore » in toluene, cyclohexane or chloroform, pristine fullerenes penetrated deeply into the stratum corneum, the primary barrier of skin. More C{sub 60} was detected in the stratum corneum when dosed in chloroform compared to toluene or cyclohexane. Fullerenes were not detected in the skin when dosed in mineral oil. This is the first direct evidence of solvent effects on the skin penetration of pristine fullerenes. The penetration of C{sub 60} into the stratum corneum was verified using isolated stratum corneum in vitro; the solvent effects on the stratum corneum absorption of C{sub 60} were consistent with those observed in vivo. In vitro flow-through diffusion cell experiments were conducted in pig skin and fullerenes were not detected in the receptor solutions by 24 h. The limit of detection was 0.001 mug/mL of fullerenes in 2 mL of the receptor solutions.« less

Development of a HPLC method for determination of four UV filters in sunscreen and its application to skin penetration studies.

PubMed

Souza, Carla; Maia Campos, Patrícia M B G

2017-12-01

This study describes the development, validation and application of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of the in vitro skin penetration profile of four UV filters on porcine skin. Experiments were carried out on a gel-cream formulation containing the following UV filters: diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) and ethylhexyl triazone (EHT). The HPLC method demonstrated suitable selectivity, linearity (10.0-50.0 μg/mL), precision, accuracy and recovery from porcine skin and sunscreen formulation. The in vitro skin penetration profile was evaluated using Franz vertical diffusion cells for 24 h after application on porcine ear skin. None of the UV filters penetrated the porcine skin. Most of them stayed on the skin surface (>90%) and only BEMT, EHT and DHHB reached the dermis plus epidermis layer. These results are in agreement with previous results in the literature. Therefore, the analytical method was useful to evaluate the in vitro skin penetration of the UV filters and may help the development of safer and effective sunscreen products. Copyright © 2017 John Wiley & Sons, Ltd.

A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies.

PubMed

Gulson, Brian; McCall, Maxine J; Bowman, Diana M; Pinheiro, Teresa

2015-11-01

Metal oxide nanoparticles in sunscreens provide broad-spectrum ultraviolet protection to skin. All studies to assess dermal penetration of nanoparticles have unanimously concluded that the overwhelming majority of nanoparticles remain on the outer surface of the skin. However, possibly due to many different experimental protocols in use, conclusions over the potential penetration to viable skin are mixed. Here, we review several factors that may influence experimental results for dermal penetration including the species studied (human, or animal model), size and coating of the metal oxide nanoparticles, composition of the sunscreen formulation, site of sunscreen application, dose and number of applications, duration of the study, types of biological samples analysed, methods for analysing samples, exposure to UV and skin flexing. Based on this information, we suggest an appropriate research agenda involving international collaboration that maximises the potential for dermal absorption of nanoparticles, and their detection, under normal conditions of sunscreen use by humans. If results from this research agenda indicate no absorption is observed, then concerns over adverse health effects from the dermal absorption of nanoparticles in sunscreens may be allayed.

Skin penetration studies of Arnica preparations and of their sesquiterpene lactones.

PubMed

Wagner, Steffen; Suter, Andreas; Merfort, Irmgard

2004-10-01

Alcoholic preparations of Arnica montana are widely used for the topical treatment of various inflammatory diseases. Sesquiterpene lactones (SLs) are mainly responsible for their anti-inflammatory activity. Here we have studied the penetration kinetics of Arnica tinctures prepared from dried Arnica flowers originating from different chemotypes as well as of their respective dominating SLs, helenalin isobutyrate and 11alpha,13-dihydrohelenalin acetate. Some alcoholic preparations of fresh Arnica flowers and an Arnica fresh plant gel were also included in the study. We used the stripping method with adhesive tape and pig skin as a model and determined the quantity of SLs in the stripped layers of the stratum corneum (SC). Thus, we observed the penetration into and permeation through this uppermost part of the skin. Whereas isolated SLs permeate through the SC only in a very small amount, permeation of SLs was much higher when they were present in the tinctures. Furthermore, differences of permeation were observed between helenalin and dihydrohelenalin derivatives. Permeation through the SC could be determined for the tested Arnica preparations of fresh Arnica flowers with two preparations showing the best penetration behaviour of all the tested substances. Moreover, the effects of incubation time as well as of repeated applications were investigated with one preparation. Altogether, this study shows that a sufficient amount of SLs might permeate the skin barrier by using Arnica preparations to exert anti-inflammatory effects and that the topical use of plant preparations may be advantageous compared to the isolated compounds.

Effect of ionization and vehicle on skin absorption and penetration of azelaic acid.

PubMed

Li, Nan; Wu, Xiaohong; Jia, Weibu; Zhang, Michelle C; Tan, Fengping; Zhang, Jerry

2012-08-01

The aim of this study is to investigate the effect of ionization and vehicle of topical formulations on skin absorption and penetration of azelaic acid (AZA). In vitro transport of AZA was determined for two topical formulations containing AZA with pH values of 3.9 and 4.9, respectively. FINACEA(®) (15% AZA gel), a US Food and Drug Administration approved drug for treatment of acne and rosacea, was also used for comparison. Release profile and flux of AZA were determined in an in vitro hairless mouse skin model using Franz Diffusion Cell. The data have shown that a higher concentration of AZA is retained in the epidermis/dermis layer and the whole skin for the formulation with pH = 4.9 as compared to that with pH = 3.9 at an active loading level of 2.82 mg/cm(2). In addition, the flux of ionized species of AZA in the pH 4.9 formulation (128.4 ± 35.9 μg/cm(2)/h) is approximately five-fold greater than that in the pH 3.9 formulation (27.7 ± 4.0 μg/cm(2)/h). The results suggest that the ionized AZA penetrates through the skin and accounts for majority of the total flux. This study has demonstrated that the penetration and absorption of AZA show a strong pH- and vehicle-dependency. Solubilization is the rate-limiting step in percutaneous absorption of AZA.

Effect of Size, Surface Charge, and Hydrophobicity of Poly(amidoamine) Dendrimers on Their Skin Penetration

PubMed Central

Yang, Yang; Sunoqrot, Suhair; Stowell, Chelsea; Ji, Jingli; Lee, Chan-Woo; Kim, Jin Woong; Khan, Seema A.; Hong, Seungpyo

2012-01-01

The barrier functions of the stratum corneum (SC) and the epidermal layers present a tremendous challenge in achieving effective transdermal delivery of drug molecules. Although a few reports have shown that poly(amidoamine) (PAMAM) dendrimers are effective skin penetration enhancers, little is known regarding the fundamental mechanisms behind the dendrimer-skin interactions. In this paper, we have performed a systematic study to better elucidate how dendrimers interact with skin layers depending on their size and surface groups. Franz diffusion cells and confocal microscopy were employed to observe dendrimer interactions with full-thickness porcine skin samples. We have found that smaller PAMAM dendrimers (generation 2 (G2)) penetrate the skin layers more efficiently than the larger ones (G4). We have also found that G2 PAMAM dendrimers that are surface modified by either acetylation or carboxylation exhibit increased skin permeation and likely diffuse through an extracellular pathway. In contrast, amine-terminated dendrimers show enhanced cell internalization and skin retention but reduced skin permeation. In addition, conjugation of oleic acid (OA) to G2 dendrimers increases their 1-octanol/PBS partition coefficient, resulting in increased skin absorption and retention. Here we report that size, surface charge, and hydrophobicity directly dictate the permeation route and efficiency of dendrimer translocation across the skin layers, providing a design guideline for engineering PAMAM dendrimers as a potential transdermal delivery vector. PMID:22621160

Penetration and decontamination of americium-241 ex vivo using fresh and frozen pig skin.

PubMed

Tazrart, A; Bolzinger, M A; Moureau, A; Molina, T; Coudert, S; Angulo, J F; Briancon, S; Griffiths, N M

2017-04-01

Skin contamination is one of the most probable risks following major nuclear or radiological incidents. However, accidents involving skin contamination with radionuclides may occur in the nuclear industry, in research laboratories and in nuclear medicine departments. This work aims to measure the penetration of the radiological contaminant Americium ( 241 Am) in fresh and frozen skin and to evaluate the distribution of the contamination in the skin. Decontamination tests were performed using water, Fuller's earth and diethylene triamine pentaacetic acid (DTPA), which is the recommended treatment in case of skin contamination with actinides such as plutonium or americium. To assess these parameters, we used the Franz cell diffusion system with full-thickness skin obtained from pigs' ears, representative of human skin. Solutions of 241 Am were deposited on the skin samples. The radioactivity content in each compartment and skin layers was measured after 24 h by liquid scintillation counting and alpha spectrophotometry. The Am cutaneous penetration to the receiver compartment is almost negligible in fresh and frozen skin. Multiple washings with water and DTPA recovered about 90% of the initial activity. The rest remains fixed mainly in the stratum corneum. Traces of activity were detected within the epidermis and dermis which is fixed and not accessible to the decontamination. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

PubMed

Choi, J H; Shin, E J; Jeong, K H; Shin, M K

2017-11-01

Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm 2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO 2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO 2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO 2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

Skin pre-ablation and laser assisted microjet injection for deep tissue penetration.

PubMed

Jang, Hun-Jae; Yeo, Seonggu; Yoh, Jack J

2017-04-01

For conventional needless injection, there still remain many unresolved issues such as the potential for cross-contamination, poor reliability of targeted delivery dose, and significantly painstaking procedures. As an alternative, the use of microjets generated with Er:YAG laser for delivering small doses with controlled penetration depths has been reported. In this study, a new system with two stages is evaluated for effective transdermal drug delivery. First, the skin is pre-ablated to eliminate the hard outer layer and second, laser-driven microjet penetrates the relatively weaker and freshly exposed epidermis. Each stage of operation shares a single Er:YAG laser that is suitable for skin ablation as well as for the generation of a microjet. In this study, pig skin is selected for quantification of the injection depth based on the two-stage procedure, namely pre-ablation and microjet injection. The three types of pre-ablation devised here consists of bulk ablation, fractional ablation, and fractional-rotational ablation. The number of laser pulses are 12, 18, and 24 for each ablation type. For fractional-rotational ablation, the fractional beams are rotated by 11.25° at each pulse. The drug permeation in the skin is evaluated using tissue marking dyes. The depth of penetration is quantified by a cross sectional view of the single spot injections. Multi-spot injections are also carried out to control the dose and spread of the drug. The benefits of a pre-ablation procedure prior to the actual microjet injection to the penetration is verified. The four possible combinations of injection are (a) microjet only; (b) bulk ablation and microjet injection; (c) fractional ablation and microjet injection; and (d) fractional-rotational ablation and microjet injection. Accordingly, the total depth increases with injection time for all cases. In particular, the total depth of penetration attained via fractional pre-ablation increased by 8 ∼ 11% and that of fractional

Photoacoustic evaluation of the penetration of piroxicam gel applied with phonophoresis into human skin

NASA Astrophysics Data System (ADS)

Silveira, F. L. F. D.; Barja, P. R.; Acosta-Avalos, D.

2010-03-01

The photoacoustic (PA) technique has been increasingly employed in biomedical studies, allowing in vivo skin measurements not easily performed with other techniques. It is possible to use PA measurements to evaluate transdermal delivery of products topically applied through manual massage or phonophoresis, that is the utilization of ultrasound waves to enhance drug absorption. The aim of this study was to analyze the influence of the period of phonophoresis application in the transdermal penetration of piroxicam gel. In vivo PA measurements employed a tungsten lamp as light source and a thin aluminum foil closing the PA chamber. The PA signals of the arm (i) clean; and (ii) after phonophoresis were utilized to estimate the concentration of piroxicam into skin. For all (4) volunteers, drug concentration in skin after phonophoresis application was the same for the different application times employed; in this way, phonophoresis for one minute seemed to be sufficient to enhance piroxicam penetration into skin. The actual amount of drug delivered into tissue depends on the person, suggesting a dependency with the skin type, which affects the PA signal level [2]. We conclude that drug delivery depends not only on the application method, but also on the specific skin type.

Formulation design for topical drug and nanoparticle treatment of skin disease.

PubMed

Raphael, Anthony P; Garrastazu, Gabriela; Sonvico, Fabio; Prow, Tarl W

2015-02-01

The skin has evolved to resist the penetration of foreign substances and particles. Topical therapeutic and cosmeceutical delivery is a growing field founded on selectively overcoming this barrier. Both the biology of the skin and the nature of the formulation/active ingredient must be aligned for efficient transcutaneous delivery. This review discusses the biological changes in the skin barrier that occur with common dermatological conditions. This context is the foundation for the discussion of formulation strategies to improve penetration profiles of common active ingredients in dermatology. Finally, we compare and contrast those approaches to recent advances described in the research literature with an eye toward the future of topical formulation design.

Nuclear microprobe investigation of the penetration of ultrafine zinc oxide into intact and tape-stripped human skin

NASA Astrophysics Data System (ADS)

Szikszai, Z.; Kertész, Zs.; Bodnár, E.; Major, I.; Borbíró, I.; Kiss, Á. Z.; Hunyadi, J.

2010-06-01

Ultrafine metal oxides, such as titanium dioxide and zinc oxide are widely used in cosmetic and health products like sunscreens. These oxides are potent UV filters and the small particle size makes the product more transparent compared to formulations containing coarser particles. In the present work the penetration of ultrafine zinc oxide into intact and tape-stripped human skin was investigated using nuclear microprobe techniques, such as proton induced X-ray spectroscopy and scanning transmission ion microscopy. Our results indicate that the penetration of ultrafine zinc oxide, in a hydrophobic basis gel with 48 h application time, is limited to the stratum corneum layer of the intact skin. Removing the stratum corneum partially or entirely by tape-stripping did not cause the penetration of the particles into the deeper dermal layers; the zinc particles remained on the surface of the skin.

The effects of sulfur mustard exposure and freezing on transdermal penetration of tritiated water through ex vivo pig skin.

PubMed

Payne, O J; Graham, S J; Dalton, C H; Spencer, P M; Mansson, R; Jenner, J; Azeke, J; Braue, E

2013-02-01

The percutaneous absorption of tritiated water ((3)H(2)O) through sulfur mustard (SM) exposed abdominal pig skin was measured using in vitro Franz-type static diffusion cells. The barrier function to water permeation following exposure to liquid SM for 8 min and excision 3h later did not change significantly. A small, but statistically significant difference (P<0.05) in steady state penetration (Jss), permeability coefficient (Kp) and lag time (t(L)) of (3)H(2)O was observed between fresh skin and skin stored frozen (-20 °C) for up to two weeks. Steady-state penetration and Kp values were significantly higher (P < 0.05) in skin stored frozen compared with fresh skin. Fresh naïve skin had an average Kp of 1.65 × 10(-3) cm h(-1), whereas frozen naïve skin was 2.04 × 10(-3) cm h(-1). Fresh SM exposed skin had a mean Kp of 1.72 × 10(-3) cm h(-1), whereas frozen SM exposed skin was 2.31 × 10(-3) cm h(-1). Lag times were also shorter (P<0.05) in skin that had been stored frozen. Frozen, SM-exposed porcine abdominal skin may be used for in vitro penetration studies, but effects of treatment and storage on the barrier layer should be taken into account. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dosimeter for measuring skin dose and more deeply penetrating radiation

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1981-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with netruon-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Microfluidic co-culture devices to assess penetration of nanoparticles into cancer cell mass.

PubMed

Jarvis, Maria; Arnold, Michael; Ott, Jenna; Pant, Kapil; Prabhakarpandian, Balabhaskar; Mitragotri, Samir

2017-09-01

In vitro and in vivo assessment of safety and efficacy are the essential first steps in developing nanoparticle-based therapeutic systems. However, it is often challenging to use the knowledge gained from in vitro studies to predict the outcome of in vivo studies since the complexity of the in vivo environment, including the existence of flow and a multicellular environment, is often lacking in traditional in vitro models. Here, we describe a microfluidic co-culture model comprising 4T1 breast cancer cells and EA.hy926 endothelial cells under physiological flow conditions and its utilization to assess the penetration of therapeutic nanoparticles from the vascular compartment into a cancerous cell mass. Camptothecin nanocrystals (∼310 nm in length), surface-functionalized with PEG or folic acid, were used as a test nanocarrier. Camptothecin nanocrystals exhibited only superficial penetration into the cancerous cell mass under fluidic conditions, but exhibited cytotoxicity throughout the cancerous cell mass. This likely suggests that superficially penetrated nanocrystals dissolve at the periphery and lead to diffusion of molecular camptothecin deep into the cancerous cell mass. The results indicate the potential of microfluidic co-culture devices to assess nanoparticle-cancerous cell interactions, which are otherwise difficult to study using standard in vitro cultures.

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

Improved penetration of wild ginseng extracts into the skin using low-temperature atmospheric pressure plasma

NASA Astrophysics Data System (ADS)

Nam, Seoul Hee; Hae Choi, Jeong; Song, Yeon Suk; Lee, Hae-June; Hong, Jin-Woo; Kim, Gyoo Cheon

2018-04-01

Wild ginseng (WG) is a well-known traditional medicinal plant that grows in natural environments in deep mountains. WG has been thought to exert potent physiological and medicinal effects, and, recently, its use in skin care has attracted much interest. This study investigated the efficient penetration of WG extracts into the skin by means of low-temperature atmospheric pressure plasma (LTAPP), and its effects on the skin at the cellular and tissue levels. NIH3T3 mouse embryonic fibroblasts and HRM-2 hairless mice were used to confirm the improved absorption of WG extracts into the skin using LTAPP. The gene expression levels in NIH3T3 cells and morphological changes in skin tissues after WG treatment were monitored using both in vitro and in vivo experiments. Although WG extracts did not show any significant effects on proliferative activity and cytotoxicity, at a concentration of 1:800, it significantly increased the expression of fibronectin and vascular endothelial growth factor. In the in vivo study, the combinational treatment of LTAPP and WG markedly induced the expression of fibronectin and integrin α6, and it thickened. Our results showed that LTAPP treatment safely and effectively accelerated the penetration of the WG extracts into the skin, thereby increasing the effects of WG on the skin.

Development of transethosomes formulation for dermal fisetin delivery: Box-Behnken design, optimization, in vitro skin penetration, vesicles-skin interaction and dermatokinetic studies.

PubMed

Moolakkadath, Thasleem; Aqil, Mohd; Ahad, Abdul; Imam, Syed Sarim; Iqbal, Babar; Sultana, Yasmin; Mujeeb, Mohd; Iqbal, Zeenat

2018-05-07

The present study was conducted for the optimization of transethosomes formulation for dermal fisetin delivery. The optimization of the formulation was carried out using "Box-Behnken design". The independent variables were Lipoid S 100, ethanol and sodium cholate. The prepared formulations were characterized for vesicle size, entrapment efficiency and in vitro skin penetration study. The vesicles-skin interaction, confocal laser scanning microscopy and dermatokinetic studies were performed with optimized formulation. Results of the present study demonstrated that the optimized formulation presented vesicle size of 74.21 ± 2.65 nm, zeta potential of -11.0 mV, entrapment efficiency of 68.31 ± 1.48% and flux of 4.13 ± 0.17 µg/cm 2 /h. The TEM image of optimized formulation exhibited sealed and spherical shape vesicles. Results of thermoanalytical techniques demonstrated that the prepared transethosomes vesicles formulation had fluidized the rigid membrane of rat's skin for smoother penetration of fisetin transethosomes. The confocal study results presented well distribution and penetration of Rhodamine B loaded transethosomes vesicles formulation up to deeper layers of the rat's skin as compared to the Rhodamine B-hydro alcoholic solution. Present study data revealed that the developed transethosomes vesicles formulation was found to be a potentially useful drug carrier for fisetin dermal delivery.

A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles.

PubMed

Islam, Mohammad Aminul; Barua, Sutapa; Barua, Dipak

2017-11-25

Particle size is a key parameter for drug-delivery nanoparticle design. It is believed that the size of a nanoparticle may have important effects on its ability to overcome the transport barriers in biological tissues. Nonetheless, such effects remain poorly understood. Using a multiscale model, this work investigates particle size effects on the tissue distribution and penetration efficacy of drug-delivery nanoparticles. We have developed a multiscale spatiotemporal model of nanoparticle transport in biological tissues. The model implements a time-adaptive Brownian Dynamics algorithm that links microscale particle-cell interactions and adhesion dynamics to tissue-scale particle dispersion and penetration. The model accounts for the advection, diffusion, and cellular uptakes of particles. Using the model, we have analyzed how particle size affects the intra-tissue dispersion and penetration of drug delivery nanoparticles. We focused on two published experimental works that investigated particle size effects in in vitro and in vivo tissue conditions. By analyzing experimental data reported in these two studies, we show that particle size effects may appear pronounced in an in vitro cell-free tissue system, such as collagen matrix. In an in vivo tissue system, the effects of particle size could be relatively modest. We provide a detailed analysis on how particle-cell interactions may determine distribution and penetration of nanoparticles in a biological tissue. Our work suggests that the size of a nanoparticle may play a less significant role in its ability to overcome the intra-tissue transport barriers. We show that experiments involving cell-free tissue systems may yield misleading observations of particle size effects due to the absence of advective transport and particle-cell interactions.

Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells

PubMed Central

Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce

2015-01-01

The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO2) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO2 nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO2 nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μg/cm2 induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO2 nanoparticles induced serious forms of DNA damage such as chromatid breaks, isochromatid lesions or chromatid exchanges. Treatments of 0, 10, 50 and 100 μg/cm2 induced 3.3, 3.0, 3.0 and 2.7% metaphases with damage, respectively. No isochromatid lesions or chromatid exchanges were detected. These data show that TiO2 nanoparticles are not cytotoxic or clastogenic to human skin cells. PMID:26568896

Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells.

PubMed

Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce

2014-11-01

The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO 2 ) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO 2 nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO 2 nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μg/cm 2 induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO 2 nanoparticles induced serious forms of DNA damage such as chromatid breaks, isochromatid lesions or chromatid exchanges. Treatments of 0, 10, 50 and 100 μg/cm 2 induced 3.3, 3.0, 3.0 and 2.7% metaphases with damage, respectively. No isochromatid lesions or chromatid exchanges were detected. These data show that TiO 2 nanoparticles are not cytotoxic or clastogenic to human skin cells.

Dermal miconazole nitrate nanocrystals - formulation development, increased antifungal efficacy & skin penetration.

PubMed

Pyo, Sung Min; Hespeler, David; Keck, Cornelia M; Müller, Rainer H

2017-10-05

Miconazole nitrate nanosuspension was developed to increase its antifungal activity and dermal penetration. In addition, the nanosuspension was combined with the synergistic additive chlorhexidine digluconate. The production was performed by wet bead milling and both production and formulation parameters were optimized. A stabilizer screening revealed poloxamer 407 and Tween 80 both at 0.15% as the most effective stabilizers for miconazole nanosuspensions at 1.0%. The nanocrystals were incorporated into a hydroxypropyl cellulose gel base. Short-term stability (3months) of the nanocrystal bulk population could be shown at room temperature and fridge. Besides the stable bulk nanocrystals, some longitudinal crystal growth to needle like crystals occurred. The addition of ionic compounds as the chlorhexidine digluconate often destabilizes suspensions. Surprisingly here, the addition minimized the crystal growth. An underlying mechanism is proposed. An inhibition zone assay was performed using Candida albicans (ATCC ® 10231™). When comparing the nanocrystals in suspension and in gel to μm-sized miconazole nitrate formulations and two market products, the increase in inhibition zone diameter for the nanosuspension formulations was most pronounced in the chlorhexidine digluconate free formulations. These nanocrystal formulations were closely or similarly effective as the microsuspensions and the market products containing the synergistic chlorhexidine digluconate, showing the potential of the nanosuspension formulation. Nanosuspension performance was even further increased when chlorhexidine digluconate was added. Ex-vivo skin penetration studies on porcine ears revealed distinctly less remaining miconazole nitrate on the skin surface for nanocrystals (e.g., 76-86%) compared to market products (e.g. 94%). Also, penetration was increased e.g. in skin depth of 5-10μm from <1.0/1.7% to e.g. 3.3-6.2% for nanocrystals. Copyright © 2017 Elsevier B.V. All rights reserved.

Tattoo ink nanoparticles in skin tissue and fibroblasts

PubMed Central

Twigg, Peter C; Baker, Richard; Tobin, Desmond J

2015-01-01

Summary Tattooing has long been practised in various societies all around the world and is becoming increasingly common and widespread in the West. Tattoo ink suspensions unquestionably contain pigments composed of nanoparticles, i.e., particles of sub-100 nm dimensions. It is widely acknowledged that nanoparticles have higher levels of chemical activity than their larger particle equivalents. However, assessment of the toxicity of tattoo inks has been the subject of little research and ink manufacturers are not obliged to disclose the exact composition of their products. This study examines tattoo ink particles in two fundamental skin components at the nanometre level. We use atomic force microscopy and light microscopy to examine cryosections of tattooed skin, exploring the collagen fibril networks in the dermis that contain ink nanoparticles. Further, we culture fibroblasts in diluted tattoo ink to explore both the immediate impact of ink pigment on cell viability and also to observe the interaction between particles and the cells. PMID:26171294

The influence of corneocyte structure on the interpretation of permeation profiles of nanoparticles across skin

NASA Astrophysics Data System (ADS)

Pinheiro, T.; Pallon, J.; Alves, L. C.; Veríssimo, A.; Filipe, P.; Silva, J. N.; Silva, R.

2007-07-01

The permeability of skin to nanoparticles of titanium dioxide (TiO 2) used in sunscreens as a reflector of the UV wavelengths of sunlight, was examined using nuclear microscopy techniques. Special attention was given to the permeation characteristics of these nanoparticles across the outer layers of skin, the stratum corneum, in healthy and psoriatic skin condition. Aspects that may influence the interpretation of results such as sample preparation difficulties and skin condition were focused. Sample preparation can damage the integrity of the corneocyte layers inducing unwanted artefacts that may bias the evaluation of results. Irradiation conditions may also introduce distortions in the labile structures of human skin. Skin condition, such as loss of corneocyte cohesion occurring in psoriasis also influence the permeation profile of the nanoparticles. Weighing and accounting for these features in the examination of skin by nuclear microscopy is crucial to accurately assess the TiO 2 nanoparticles permeation depth.

Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for Skin Sensitization

EPA Science Inventory

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW < 500, are assumed and widely accepted as self-evident truths. Objective...

Investigation of follicular and non-follicular pathways for polyarginine and oleic acid modified nanoparticles

PubMed Central

Hayden, Patrick; Singh, Mandip

2013-01-01

Purpose The aim of the current study was to investigate the percutaneous permeation pathways of cell penetrating peptide modified lipid nanoparticles and oleic acid modified polymeric nanoparticles. Methods Confocal microscopy was performed on skin cultures (EpiDermFT™) for modified and un-modified nanoparticles. Differential stripping was performed following in vitro skin permeation of Ibuprofen (Ibu) encapsulated nanoparticles to estimate Ibu levels in different skin layers and receiver compartment. The hair follicles (HF) were blocked and in vitro skin permeation of nanoparticles was then compared with unblocked HF. The surface modified nanoparticles were investigated for response on allergic contact dermatitis (ACD). Results Surface modified nanoparticles showed a significant higher (p < 0.05) in fluorescence in EpiDermFT™ cultures compared to controls. The HF play less than 5% role in total nanoparticle permeation into the skin. The Ibu levels were significantly high (p<0.05) for surface modified nanoparticles compared to controls. The Ibu levels in skin and receiver compartment were not significantly different when HF were open or closed. Modified nanoparticles showed significant improvement in treatment of ACD compared to solution. Conclusions Our studies demonstrate that increased skin permeation of surface modified nanoparticles is not only dependent on a follicular pathway but also occur through non-follicular pathway(s). PMID:23187866

Glove material, reservoir formation, and dose affect glove permeation and subsequent skin penetration.

PubMed

Nielsen, Jesper Bo; Sørensen, Jens Ahm

2012-02-15

Protective gloves are used to reduce dermal exposure when managing chemical exposures at the work place. Different glove materials may offer different degrees of protection. The present study combined the traditional ASTM (American Society for Testing and Materials) model with the Franz diffusion cell to evaluate overall penetration through glove and skin as well as the deposition in the different reservoirs. Benzoic acid was applied on latex or nitrile gloves placed on top of human skin. The amounts of chemical were quantified in the glove material, between glove and skin, within the skin, and in the receptor chamber. Both glove materials reduce total penetration of benzoic acid, but nitrile gloves offer a significantly better protection than latex gloves. This difference was less pronounced at the higher of the two concentrations of benzoic acid applied. Thus, glove types that offer relevant protection at low concentrations does not necessarily give appropriate protection at high concentrations. Significant amounts of benzoic acid could be extracted from the glove materials after exposure. If a chemical is accumulated in the glove material, reuse of single-use gloves should be cautioned. The reuse of gloves is generally not to be recommended without effective decontamination. Copyright © 2011 Elsevier B.V. All rights reserved.

Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy.

PubMed

Hu, Chuan; Cun, Xingli; Ruan, Shaobo; Liu, Rui; Xiao, Wei; Yang, Xiaotong; Yang, Yuanyuan; Yang, Chuanyao; Gao, Huile

2018-06-01

Chemotherapy remains restricted by poor drug delivery efficacy due to the heterogenous nature of tumor. Herein, we presented a novel nanoparticle that could not only response to the tumor microenvironment but also modulate it for deep tumor penetration and combination therapy. The intelligent nanoparticle (IDDHN) was engineered by hyaluronidase (HAase)-triggered size shrinkable hyaluronic acid shells, which were modified with NIR laser sensitive nitric oxide donor (HN), small-sized dendrimeric prodrug (IDD) of doxorubicin (DOX) as chemotherapy agent and indocyanine green (ICG) as photothermal agent into a single nanoparticle. IDDHN displayed synergistic deep penetration both in vitro and in vivo, owing to the enzymatically degradable HN shell mediated by HAase and laser-enhanced NO release triggered deep penetration upon strong hyperthermia effect of ICG under the NIR laser irradiation. The therapeutic effect of IDDHN was verified in 4T1 xenograft tumor model, and IDDHN showed a much better antitumor efficiency with few side effects upon NIR laser irradiation. Therefore, the valid of this study might provide a novel tactic for engineering nanoparticles both response to and modulate the tumor microenvironment for improving penetration and heterogeneity distribution of therapeutic agents in tumor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Roxithromycin-loaded lipid nanoparticles for follicular targeting.

PubMed

Wosicka-Frąckowiak, Hanna; Cal, Krzysztof; Stefanowska, Justyna; Główka, Eliza; Nowacka, Magdalena; Struck-Lewicka, Wiktoria; Govedarica, Biljana; Pasikowska, Monika; Dębowska, Renata; Jesionowski, Teofil; Srčič, Stane; Markuszewski, Michał Jan

2015-11-30

Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm. Copyright © 2015 Elsevier B.V. All rights reserved.

Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies

PubMed Central

Cross, Sheree E; Anderson, Chris; Roberts, Michael S

1998-01-01

Aims The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site. Methods The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes. Results The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels of salicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations. Conclusion The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply. PMID:9690946

Palladium and Platinum Nanoparticles Attenuate Aging-Like Skin Atrophy via Antioxidant Activity in Mice

PubMed Central

Shibuya, Shuichi; Ozawa, Yusuke; Watanabe, Kenji; Izuo, Naotaka; Toda, Toshihiko; Yokote, Koutaro; Shimizu, Takahiko

2014-01-01

Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including skin atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related skin pathologies in mice. Transdermal PAPLAL treatment reversed skin thinning associated with increased lipid peroxidation in Sod1 −/− mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the skin of the Sod1 −/− mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related skin diseases caused by oxidative damage. PMID:25333617

Palladium and platinum nanoparticles attenuate aging-like skin atrophy via antioxidant activity in mice.

PubMed

Shibuya, Shuichi; Ozawa, Yusuke; Watanabe, Kenji; Izuo, Naotaka; Toda, Toshihiko; Yokote, Koutaro; Shimizu, Takahiko

2014-01-01

Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including skin atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related skin pathologies in mice. Transdermal PAPLAL treatment reversed skin thinning associated with increased lipid peroxidation in Sod1-/- mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the skin of the Sod1-/- mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related skin diseases caused by oxidative damage.

Bio-stimuli-responsive multi-scale hyaluronic acid nanoparticles for deepened tumor penetration and enhanced therapy.

PubMed

Huo, Mengmeng; Li, Wenyan; Chaudhuri, Arka Sen; Fan, Yuchao; Han, Xiu; Yang, Chen; Wu, Zhenghong; Qi, Xiaole

2017-09-01

In this study, we developed bio-stimuli-responsive multi-scale hyaluronic acid (HA) nanoparticles encapsulated with polyamidoamine (PAMAM) dendrimers as the subunits. These HA/PAMAM nanoparticles of large scale (197.10±3.00nm) were stable during systematic circulation then enriched at the tumor sites; however, they were prone to be degraded by the high expressed hyaluronidase (HAase) to release inner PAMAM dendrimers and regained a small scale (5.77±0.25nm) with positive charge. After employing tumor spheroids penetration assay on A549 3D tumor spheroids for 8h, the fluorescein isothiocyanate (FITC) labeled multi-scale HA/PAMAM-FITC nanoparticles could penetrate deeply into these tumor spheroids with the degradation of HAase. Moreover, small animal imaging technology in male nude mice bearing H22 tumor showed HA/PAMAM-FITC nanoparticles possess higher prolonged systematic circulation compared with both PAMAM-FITC nanoparticles and free FITC. In addition, after intravenous administration in mice bearing H22 tumors, methotrexate (MTX) loaded multi-scale HA/PAMAM-MTX nanoparticles exhibited a 2.68-fold greater antitumor activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of Surfactants on Skin Penetration of Dexpanthenol.

PubMed

Laffleur, Flavia; Pschick, Stefan; Barthelmes, Jan; Hauptstein, Sabine; Bernkop-Schnurch, Andreas

2018-01-01

It was the aim of this study to evaluate the impact of nonionic and ionic surfactants on skin penetration of dexpanthenol. The relative potency of three surfactants (two nonionic and one ionic) as enhancers in the permeability of a series of compounds was investigated. The influence of the enhancers was also studied. For this purpose, porcine abdominal skin was prepared and mounted on Franz diffusion cells, while different mixtures of Dexpanthenol containing Tween®85, SDS and Span®80 in concentrations of 0.5%, 1%, 2%, 5% (m/V) were evaluated in terms of their permeation enhancing effect. The amount of permeated drug was determined via HPLC analysis. Moreover, the cytotoxicity and skin irritating effect of the compounds were tested on Caco-2 cells. The cytotoxicity profile of Dexpanthenol showed no toxicity to the cells over 1 and 3 h of incubation. The permeation was evaluated over a time period of 180 min, whereas a ranking of SDS> Span>Tween could be determined as permeation enhancer. Taking these findings into consideration, concentration of 1% (w/w) surfactant showed the most promising results. The increase in flux based on low concentrations of enhancer was ascribed to their ability to reduce skin´s barrier and improve drug permeation. The results showed that the nature of enhancer greatly impacts cutaneous barrier impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Penetration of nanoparticles in flax (Linum usitatissimum L.) calli and regenerants.

PubMed

Kokina, Inese; Gerbreders, Vjačeslavs; Sledevskis, Eriks; Bulanovs, Andrejs

2013-05-20

We demonstrate a method for direct delivery of metal nanoparticles to flax calli and regenerant cells by vacuum deposition of metal nanolayers on powdered hormone followed by dispersal of the combined hormone-metal in medium. The penetration and location of the gold (AuNPs) and silver (AgNPs) nanoparticles in calli and in plant regenerants were confirmed by optical absorption spectroscopy and scanning electron microscopy. We detected a significant effect of the AuNPs and AgNPs on the regeneration type of flax calli. Copyright © 2013 Elsevier B.V. All rights reserved.

Use of Agave tequilana-lignin and zinc oxide nanoparticles for skin photoprotection.

PubMed

Gutiérrez-Hernández, José Manuel; Escalante, Alfredo; Murillo-Vázquez, Raquel Nalleli; Delgado, Ezequiel; González, Francisco Javier; Toríz, Guillermo

2016-10-01

The use of sunscreens is essential for preventing skin damage and the potential appearance of skin cancer in humans. Inorganic active components such as zinc oxide (ZnO) have been used commonly in sunscreens due to their ability to block UVA radiation. This ultraviolet (UV) protection might be enhanced to cover the UVB and UVC bands when combined with other components such as titanium dioxide (TiO2). In this work we evaluate the photoprotection properties of organic nanoparticles made from lignin in combination with ZnO nanoparticles as active ingredients for sunscreens. Lignin nanoparticles were synthesized from Agave tequilana lignin. Two different pulping methods were used for dissolving lignin from agave bagasse. ZnO nanoparticles were synthesized by the precipitation method. All nanoparticles were characterized by SEM, UV-Vis and FT-IR spectroscopy. Nanoparticles were mixed with a neutral vehicle in different concentrations and in-vitro sun protection factor (SPF) values were calculated. Different sizes of spherical lignin nanoparticles were obtained from the spent liquors of two different pulping methods. ZnO nanoparticles resulted with a flake shape. The mixture of all components gave SPF values in a range between 4 and 13. Lignin nanoparticles showed absorption in the UVB and UVC regions which can enhance the SPF value of sunscreens composed only of zinc oxide nanoparticles. Lignin nanoparticles have the added advantage of being of organic nature and its brown color can be used to match the skin tone of the person using it. Copyright © 2016 Elsevier B.V. All rights reserved.

Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model

PubMed Central

2014-01-01

Background Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their optical properties against the UV-light that causes dermal damage and skin cancer. However, the hazardous properties of the particles used as UV-filters in the sunscreens and applied to the skin have remained uncharacterized. Methods Here we investigated whether different sized ZnO particles would be able to penetrate injured skin and injured allergic skin in the mouse atopic dermatitis model after repeated topical application of ZnO particles. Nano-sized ZnO (nZnO) and bulk-sized ZnO (bZnO) were applied to mechanically damaged mouse skin with or without allergen/superantigen sensitization. Allergen/superantigen sensitization evokes local inflammation and allergy in the skin and is used as a disease model of atopic dermatitis (AD). Results Our results demonstrate that only nZnO is able to reach into the deep layers of the allergic skin whereas bZnO stays in the upper layers of both damaged and allergic skin. In addition, both types of particles diminish the local skin inflammation induced in the mouse model of AD; however, nZnO has a higher potential to suppress the local effects. In addition, especially nZnO induces systemic production of IgE antibodies, evidence of allergy promoting adjuvant properties for topically applied nZnO. Conclusions These results provide new hazard characterization data about the metal oxide nanoparticles commonly used in cosmetic products and provide new insights into the dermal exposure and hazard assessment of these materials in injured skin. PMID:25123235

Development of ibuprofen-loaded nanostructured lipid carrier-based gels: characterization and investigation of in vitro and in vivo penetration through the skin

PubMed Central

Sütő, Blanka; Berkó, Szilvia; Kozma, Gábor; Kukovecz, Ákos; Budai-Szűcs, Mária; Erős, Gábor; Kemény, Lajos; Sztojkov-Ivanov, Anita; Gáspár, Róbert; Csányi, Erzsébet

2016-01-01

An ibuprofen-loaded nanostructured lipid carrier (IBU-NLC) was developed for enhanced skin penetration to improve the treatment of osteoarthritis and other musculoskeletal diseases. The mean particle size was 106 nm, with a spherical morphology, a smooth surface, and a zeta potential of −18.4 mV. X-ray diffraction studies revealed the amorphous state of the lipid matrix. Both Raman spectroscopy and Fourier transformation infrared analysis indicated no major shifts in the spectra of the formulations, which suggest rapid drug dissolution from the nanoparticles. The drug loading was 9.85%, and the entrapment efficiency was 98.51%. In vitro release of the NLC dispersion, in vitro permeation, and in vivo animal studies of IBU-NLC gel all confirmed that the permeation of IBU was significantly better than that of a reference after 6 hours. In conclusion, IBU-NLC gel is of great potential to enhance drug permeation through the skin and hence the efficacy of the treatment of chronic joint inflammation. PMID:27099487

Nanoparticle-based photodynamic therapy on non-melanoma skin cancer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Arce-Diego, J. L.

2018-02-01

There are several advantages of Photodynamic Therapy (PDT) for nonmelanoma skin cancer treatment compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages its noninvasive nature, the use of non ionizing radiation and its high selectivity can be mentioned. Despite all these advantages, the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. An adequate dosimetry is needed in order to personalize the protocol. There are strategies that try to overcome the current PDT shortcomings, such as the improvement of the photosensitizer accumulation in the target tissue, optical radiation distribution optimization or photochemical reactions maximization. These strategies can be further complemented by the use of nanostructures with conventional PDT. Customized dosimetry for nanoparticle-based PDT requires models in order to adjust parameters of different nature to get an optimal tumor removal. In this work, a predictive model of nanoparticle-based PDT is proposed and analyzed. Dosimetry in nanoparticle-based PDT is going to be influenced by photosensitizer-nanoparticle distribution in the malignant tissue, its influence in the optical radiation distribution and the subsequent photochemical reactions. Nanoparticles are considered as photosensitizer carriers on several types of non-melanoma skin cancer. Shielding effects are taken into account. The results allow to compare the estimated treatment outcome with and without nanoparticles.

Dermal absorption behavior of fluorescent molecules in nanoparticles on human and porcine skin models.

PubMed

Debotton, Nir; Badihi, Amit; Robinpour, Mano; Enk, Claes D; Benita, Simon

2017-05-30

The percutaneous passage of poorly skin absorbed molecules can be improved using nanocarriers, particularly biodegradable polymeric nanospheres (NSs) or nanocapsules (NCs). However, penetration of the encapsulated molecules may be affected by other factors than the nanocarrier properties. To gain insight information on the skin absorption of two fluorescent cargos, DiIC 18 (5) and coumarin-6 were incorporated in NSs or NCs and topically applied on various human and porcine skin samples. 3D imaging techniques suggest that NSs and NCs enhanced deep dermal penetration of both probes similarly, when applied on excised human skin irrespective of the nature of the cargo. However, when ex vivo pig skin was utilized, the cutaneous absorption of DiIC 18 (5) was more pronounced by means of PLGA NCs than NSs. In contrast, PLGA NSs noticeably improved the porcine skin penetration of coumarin-6, as compared to the NCs. Furthermore, the porcine skin results were reproducible when triplicated whereas from various human skin samples, as expected, the results were not sufficiently reproducible and large deviations were observed. The overall findings from this comprehensive comparison emphasize the potential of PLGA NCs or NSs to promote cutaneous bioavailability of encapsulated drugs, exhibiting different physicochemical properties but depending on the nature of the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Double emulsions based on silicone-fluorocarbon-water and their skin penetration.

PubMed

Mahrhauser, Denise-Silvia; Fischer, Claudia; Valenta, Claudia

2016-02-10

Double emulsions have significant potential in pharmacy and cosmetics due to the feasibility of combining incompatible substances in one product and the protection of sensitive compounds by incorporating them into their innermost phase. However, a major drawback of double emulsions is their thermodynamic instability and their strong tendency to coalesce. In the present study, the physicochemical stability, the skin permeation and the skin penetration potential of modified semi-solid double emulsions was investigated. The double emulsions were prepared of the cosmetically applied perfluoropolyethers Fomblin HC/04 or Fomblin HC-OH, silicone, carbomer and water. Measurement of the droplet size and examination of the microscopic images confirmed their physicochemical stability over the observation period of eight weeks. Franz-type diffusion cell experiments revealed no increase in curcumin permeation due to the employed perfluoropolyethers compared to the respective control formulations. The formulations used as control were O/W macroemulsions with or without a Polysorbate 80/Sorbitane monooleate 80 surfactant combination. Likewise, tape stripping studies showed no penetration enhancing effect of the employed perfluoropolyethers which is desirable as both perfluoropolyethers are commonly applied components in human personal-care products. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of wellbore storage and finite thickness skin on flow to a partially penetrating well in a phreatic aquifer

NASA Astrophysics Data System (ADS)

Pasandi, M.; Samani, N.; Barry, D. A.

2008-02-01

An analytical model is presented for the analysis of constant flux tests conducted in a phreatic aquifer having a partially penetrating well with a finite thickness skin. The solution is derived in the Laplace transform domain for the drawdown in the pumping well, skin and formation regions. The time-domain solution in terms of the aquifer drawdown is then obtained from the numerical inversion of the Laplace transform and presented as dimensionless drawdown-time curves. The derived solution is used to investigate the effects of the hydraulic conductivity contrast between the skin and formation, in addition to wellbore storage, skin thickness, delayed yield, partial penetration and distance to the observation well. The results of the developed solution were compared with those from an existing solution for the case of an infinitesimally thin skin. The latter solution can never approximate that for the developed finite skin. Dimensionless drawdown-time curves were compared with the other published results for a confined aquifer. Positive skin effects are reflected in the early time and disappear in the intermediate and late time aquifer responses. But in the case of negative skin this is reversed and the negative skin also tends to disguise the wellbore storage effect. A thick negative skin lowers the overall drawdown in the aquifer and leads to more persistent delayed drainage. Partial penetration increases the drawdown in the case of a positive skin; however its effect is masked by the negative skin. The influence of a negative skin is pronounced over a broad range of radial distances. At distant observation points the influence of a positive skin is too small to be reflected in early and intermediate time pumping test data and consequently the type curve takes its asymptotic form.

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™).

PubMed

Wills, John W; Hondow, Nicole; Thomas, Adam D; Chapman, Katherine E; Fish, David; Maffeis, Thierry G; Penny, Mark W; Brown, Richard A; Jenkins, Gareth J S; Brown, Andy P; White, Paul A; Doak, Shareen H

2016-09-09

The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing. BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium. 3D dose-responses were compared to a 2D micronucleus assay using monocultured human B cells (TK6) after standardising dose between 2D / 3D assays by total nanoparticle mass to cell number. Cryogenic vitrification, scanning electron microscopy and dynamic light scattering techniques were applied to characterise in-medium and air-liquid interface exposures. Advanced transmission electron microscopy imaging modes (high angle annular dark field) and X-ray spectrometry were used to define nanoparticle penetration / cellular uptake in the intact 3D models and 2D monocultured cells. For all 2D exposures, significant (p < 0.002) increases in genotoxicity were observed (≥100 μg/mL) alongside cell viability decreases (p < 0.015) at doses ≥200 μg/mL (16 nm-SiO2) and ≥100 μg/mL (85 nm-SiO2). In contrast, 2D-equivalent exposures to the 3D models (≤300 μg/mL) caused no significant DNA damage or impact on cell viability. Further increasing dose to the 3D models led to probable air-liquid interface suffocation. Nanoparticle penetration / cell uptake analysis revealed no exposure to the live cells of the 3D model occurred due to the protective nature of the skin model's 3D cellular microarchitecture (topical exposures) and confounding barrier effects of the collagen cell attachment layer (in-medium exposures). 2D

Microwave-aided skin drug penetration and retention of 5-fluorouracil-loaded ethosomes.

PubMed

Khan, Nauman Rahim; Wong, Tin Wui

2016-09-01

Skin drug retention is required in local treatment of skin cancer. This study investigated the interplay effects of ethosomes and microwave in transdermal drug delivery. Skin pre-treatment by microwave and applied with liquified medicine is deemed to 'cement' the skin thereby raising skin drug deposition. 5-fluorouracil-loaded ethosomes were prepared and subjected to size, zeta potential, morphology, drug content, drug release and skin permeation tests. The molecular characteristics of untreated, microwave and/or ethosome-treated skins were examined by Fourier transform infrared and raman spectroscopy, thermal and electron microscopy techniques. The skin drug retention was promoted using larger ethosomes with negative zeta potentials that repelled anionic lipids of skin and hindered vesicle permeation into deep layers. These ethosomes had low ethanol content. They were less able to fluidize the lipid and defluidize the protein domains at epidermis to enlarge aqueous pores for drug permeation. Pre-treatment of skin by 2450 MHz microwave for 2.5 min further increased skin drug penetration and retention of low ethanol ethosomes and provided lower drug permeation than cases treated for 1.15 min and 5 min. A 2.5 min treatment might be accompanied by specific dermal protein fluidization via C=O moiety which translated to macromolecular swelling, narrowing of intercellular spaces at lower skin layers, increased drug retention and reduced drug permeation. Ethosomes and microwave synergized to promote skin drug retention.

De Novo Design of Skin-Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs.

PubMed

Menegatti, Stefano; Zakrewsky, Michael; Kumar, Sunny; De Oliveira, Joshua Sanchez; Muraski, John A; Mitragotri, Samir

2016-03-09

Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study of the vitamins A, E and C esters penetration into the skin by confocal Raman spectroscopy in vivo

NASA Astrophysics Data System (ADS)

Mogilevych, Borys; Isensee, Debora; Rangel, Joao L.; Dal Pizzol, Carine; Martinello, Valeska C. A.; Dieamant, Gustavo C.; Martin, Airton A.

2015-06-01

Vitamins A, E and C play important role in skin homeostasis and protection. Hence, they are extensively used in many cosmetic and cosmeceutic products. However, their molecules are unstable, and do not easily penetrate into the skin, which drastically decreases its efficiency in topical formulations. Liposoluble derivative of the vitamin A - retinyl palmitate, vitamin E - tocopheryl acetate, and vitamin C - tetraisopalmitoyl ascorbic acid, are more stable, and are frequently used as an active ingredient in cosmetic products. Moreover, increased hydrophobicity of these molecules could lead to a higher skin penetration. The aim of this work is to track and compare the absorption of the liposoluble derivatives of the vitamins and their encapsulated form, into the healthy human skin in vivo. We used Confocal Raman Spectroscopy (CRS) that is proven to be helpful in label-free non-destructive investigation of the biochemical composition and molecular conformational analysis of the biological samples. The measurements were performed in the volar forearm of the 10 healthy volunteers. Skin was treated with both products, and Raman spectra were obtained after 15 min, 3 hours, and 6 hours after applying the formulation. 3510 Skin Composition Analyzer (River Diagnostics, The Netherlands) with 785 nm laser excitation was used to acquire information in the fingerprint region. Significant difference in permeation of the products was observed. Whereas only free form of retinyl palmitate penetrate the skin within first 15 minutes, all three vitamin derivatives were present under the skin surface in case of nanoparticulated form.

Skin penetration behaviour of sesquiterpene lactones from different Arnica preparations using a validated GC-MSD method.

PubMed

Wagner, Steffen; Merfort, Irmgard

2007-01-04

Preparations of Arnica montana L. are widely used for the topical treatment of inflammatory diseases. The anti-inflammatory activity is mainly attributed to their sesquiterpene lactones (SLs) from the helenalin and 11alpha,13-dihydrohelenalin type. To study the penetration kinetics of SLs in Arnica preparations, a stripping method with adhesive tape and pig skin as a model was used. For the determination of SLs in the stripped layers of the stratum corneum (SC), a gas chromatography/mass spectrometry method was developed and validated. Thereby the amount of helenalin derivatives was calculated as helenalin isobutyrate, and 11alpha,13-dihydrohelenalin derivatives as 11alpha,13-dihydrohelenalin methacrylate. This GC-MSD method is suitable also to determine low amounts of SLs in Arnica preparations. The penetration behaviour of one gel preparation and two ointment preparations was investigated. The SLs of all preparations show a comparable penetration in and a permeation through the stratum corneum, the uppermost part of the skin. Interestingly, the gel preparation showed a decrease of the penetration rate over 4h, whereas the penetration rate of ointments kept constant over time. Moreover, we could demonstrate that the totally penetrated amount of SLs only depends on the kind of the formulation and of the SLs-content in the formulation but not on the SLs composition or on the used extraction agent.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is

Investigating skin penetration depth and shape following needle-free injection at different pressures: A cadaveric study.

PubMed

Seok, Joon; Oh, Chang Taek; Kwon, Hyun Jung; Kwon, Tae Rin; Choi, Eun Ja; Choi, Sun Young; Mun, Seog Kyun; Han, Seung-Ho; Kim, Beom Joon; Kim, Myeung Nam

2016-08-01

The effectiveness of needle-free injection devices in neocollagenesis for treating extended skin planes is an area of active research. It is anticipated that needle-free injection systems will not only be used to inject vaccines or insulin, but will also greatly aid skin rejuvenation when used to inject aesthetic materials such as hyaluronic acid, botulinum toxin, and placental extracts. There has not been any specific research to date examining how materials penetrate the skin when a needle-free injection device is used. In this study, we investigated how material infiltrates the skin when it is injected into a cadaver using a needle-free device. Using a needle-free injector (INNOJECTOR™; Amore Pacific, Seoul, Korea), 0.2 ml of 5% methylene blue (MB) or latex was injected into cheeks of human cadavers. The device has a nozzle diameter of 100 µm and produces a jet with velocity of 180 m/s. This jet penetrates the skin and delivers medicine intradermally via liquid propelled by compressed gasses. Materials were injected at pressures of 6 or 8.5 bars, and the injection areas were excised after the procedure. The excised areas were observed visually and with a phototrichogram to investigate the size, infiltration depth, and shape of the hole created on the skin. A small part of the area that was excised was magnified and stained with H&E (×40) for histological examination. We characterized the shape, size, and depth of skin infiltration following injection of 5% MB or latex into cadaver cheeks using a needle-free injection device at various pressure settings. Under visual inspection, the injection at 6 bars created semi-circle-shaped hole that penetrated half the depth of the excised tissue, while injection at 8.5 bars created a cylinder-shaped hole that spanned the entire depth of the excised tissue. More specific measurements were collected using phototrichogram imaging. The shape of the injection entry point was consistently spherical regardless of the

On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein.

PubMed

Mun, Ellina A; Morrison, Peter W J; Williams, Adrian C; Khutoryanskiy, Vitaliy V

2014-10-06

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase.

Photoacoustic Analysis of the Penetration Kinetics of Cordia verbenacea DC in Human Skin

NASA Astrophysics Data System (ADS)

Carvalho, S. S.; Barja, P. R.

2012-11-01

Phonophoresis consists of the utilization of ultrasound radiation associated to pharmacological agents in order to enhance transdermal penetration of applied drugs. It is a widely employed resource in physiotherapy practice, normally associated with anti-inflammatory drugs, such as Acheflan. This drug was developed in Brazil from the essential oil of Cordia verbenacea DC, a native plant of the Brazilian southern coast. In previous studies, the photoacoustic (PA) technique proved effective in the study of the penetration kinetics of topically applied products and in the evaluation of drug delivery after phonophoresis application. The present work aimed to evaluate the penetration kinetics of Acheflan in human skin, employing in vivo PA measurements after massage application or phonophoresis application. Ten volunteers (aged between 18 and 30 years) took part in the study. Time evolution of the PA signal was fitted to a Boltzmann curve, S-shaped. After statistical analysis, PA measurements have shown drug penetration for both application forms, but drug delivery was more evident after phonophoresis application, with a characteristic penetration time of less than 15 min for the stratum corneum.

Silica- and perfluoro-based nanoparticular polymeric network for the skin protection against organophosphates

NASA Astrophysics Data System (ADS)

Bignon, Cécile; Amigoni, Sonia; Guittard, Frédéric

2016-06-01

Due to their small size, nanoparticles possess unique properties such as high absorption or pollutant degradation, making them useful for skin protection against chemicals. By covalently grafting to a hydrophobically modified alkali-soluble emulsion (HASE), a thickening polymer, nanoparticles can be dispersed as gels in water at neutral pH. With this modification the potential aggregation and toxicity typical of nanoparticles are avoided. Once integrated into a cosmetic formula, these gels can be spread onto skin to afford protective barriers. This paper reports (1) the benefit of SiO2 nanoparticles grafted to a perfluorocarbon HASE polymer (HASE-F/SiO2) which is then integrated into a new formula and it is influence on the efficacy against the penetration of paraoxone, as well as (2) the stability of the barrier cream (BC) and (3) how the homogenous dispersion of nanoparticles maintains a high active surface area of SiO2 nanoparticles. The efficiency of the new active topical skin protectant was proved at different doses (5-27 mg cm-2), under occlusive conditions and validated on human skin. Therefore, the combination of the HASE-F polymer, nanoparticle grafting, and polyvinylpyrrolidone and glycerol formulation led to a very effective active BC.

Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

PubMed

Barbero, Ana M; Frasch, H Frederick

2009-02-01

Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (P<0.0001), with an intra species average coefficient of variation of skin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (P<0.0001), with an average intra species coefficient of variation of 19% for guinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, P<0.0001, n=12). When permeability data was not reported a factor of difference (FOD) of animal to human skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.

Skin transport of PEGylated poly(ε-caprolactone) nanoparticles assisted by (2-hydroxypropyl)-β-cyclodextrin.

PubMed

Conte, Claudia; Costabile, Gabriella; d'Angelo, Ivana; Pannico, Marianna; Musto, Pellegrino; Grassia, Gianluca; Ialenti, Armando; Tirino, Pasquale; Miro, Agnese; Ungaro, Francesca; Quaglia, Fabiana

2015-09-15

The aim of this work was to investigate the potential of small nanoparticles (NPs) made of a poly(ethylene glycol)-poly(ε-caprolactone)-amphiphilic diblock copolymer (PEG-b-PCL, PEG=2kDa and PCL=4.2kDa) as drug carrier system through the skin. Zinc(II) phthalocyanine (ZnPc), selected as lipophilic and fluorescent model molecule, was loaded inside NPs by a melting/sonication procedure. Loaded NPs with a hydrodynamic diameter around 60nm, a slightly negative zeta potential and a ZnPc entrapment dependent on polymer/ZnPc ratio were obtained. Spectroscopic investigations evidenced that ZnPc was entrapped in monomeric form maintaining its emission properties. The transport of ZnPc through porcine ear skin was evaluated on Franz-type diffusion cells after treatment with different vehicles (water or PEG 0.4kDa) containing free ZnPc or ZnPc-loaded NPs without and with (2-hydroxypropyl)-β-cyclodextrin (HPβCD) as permeation enhancer. Independently of the sample tested, ZnPc was transported in the skin without reaching receptor compartment. On the other hand, ZnPc was found in the skin in large amount and also in the viable epidermis when delivered through NPs associated with HPβCD, especially in conditions limiting water evaporation. Fluorescence images of skin samples after 24h of permeation were in line with ZnPc dosage in the skin and demonstrated the ability of NPs covalently tagged with rhodamine to penetrate the skin and to locate in the intercellular spaces. Insight into skin chemical properties upon application of NPs by confocal Raman spectroscopy demonstrated that HPβCD caused an alteration of water profile in the skin, highly reducing the degree of hydration at stratum corneum/viable epidermis interface which can promote NP transport. Taken together, these results highlight PEG-b-PCL NPs coupled with HPβCD as a novel vehicle for the skin delivery of highly lipophilic compounds paving the way to several applications. Copyright © 2015 Elsevier Inc. All rights

DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

PubMed

Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

2015-01-01

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

Self-Assembled Cubic Liquid Crystalline Nanoparticles for Transdermal Delivery of Paeonol

PubMed Central

Li, Jian-Chun; Zhu, Na; Zhu, Jin-Xiu; Zhang, Wen-Jing; Zhang, Hong-Min; Wang, Qing-Qing; Wu, Xiao-Xiang; Wang, Xiu; Zhang, Jin; Hao, Ji-Fu

2015-01-01

Background The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. Material/Methods In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment. In vitro tests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in the in vitro penetration and retention experiments both was determined quantitatively by HPLC. Results Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. Conclusions The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application. PMID:26517086

Coadministration of iRGD with Multistage Responsive Nanoparticles Enhanced Tumor Targeting and Penetration Abilities for Breast Cancer Therapy.

PubMed

Hu, Chuan; Yang, Xiaotong; Liu, Rui; Ruan, Shaobo; Zhou, Yang; Xiao, Wei; Yu, Wenqi; Yang, Chuanyao; Gao, Huile

2018-06-21

Limited tumor targeting and poor penetration of nanoparticles are two major obstacles to improving the outcome of tumor therapy. Herein, coadministration of tumor-homing peptide iRGD and multistage-responsive penetrating nanoparticles for the treatment of breast cancer are reported. This multistage-responsive nanoparticle, IDDHN, was comprised of an NO donor-modified hyaluronic acid (HN) shell and a small-sized dendrimer, namely, dendri-graft-l-lysine conjugated with doxorubicin and indocyanine (IDD). The results showed that IDDHN could be degraded rapidly from about 330 nm to a smaller size that was in a size range of 35 to 150 nm (most at 35-60 nm) after hyaluronidase (HAase) incubation for 4 h; in vitro cellular uptake demonstrated that iRGD could mediate more endocytosis of IDDHN into 4T1 cells, which was attributed to the overexpression of α v β 3 integrin receptor. Multicellular spheroids penetration results showed synergistically enhanced deeper distribution of IDDHN into tumors, with the presence of iRGD, HAase incubation, and NO release upon laser irradiation. In vivo imaging indicated that coadministration with iRGD markedly enhanced the tumor targeting and penetration abilities of IDDHN. Surprisingly, coadministration of IDDHN with iRGD plus 808 nm laser irradiation nearly suppressed all tumor growth. These results systematically revealed the excellent potential of coadministration of iRGD with multistage-responsive nanoparticles for enhancing drug delivery efficiency and overcoming the 4T1 breast cancer.

Feasibility of Human Skin Grafts on an Isolated but Accessible Vascular Supply on Athymic Rats as a System to Study Percutaneous Penetration and Cutaneous Injury.

DTIC Science & Technology

1983-11-01

HUMAN SKIN GRAFTS ON AN ISOLATED BUT ACCESSIBLE VASCULAR SUPPLY ON ATHYMIC RATS AS A SYSTEM TO STUDY PERCUTANEOUS PENETRATION AND CUTANEOUS INJURY...RECIPIENT’S CATALOG NUMBER 4. TITLE (aend Subtitle) S. TYPE OF REPORT & PERIOD COVERED Feasibility of Human Skin Grafts on an Isolated Annual report...Human skin graft on athymic rat Human skin model to study percutaneous penetration and cutaneous injury 20. ABSTRACT (Contiue an reverse *ftb it

Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

PubMed

Lauterbach, Andreas; Müller-Goymann, Christel C

2015-11-01

Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle targeting.

PubMed

Fernandes, B; Silva, R; Ribeiro, A; Matamá, T; Gomes, A C; Cavaco-Paulo, A M

2015-06-01

Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery. Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively. Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts. The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release

Protective effect of maghemite nanoparticles on ultraviolet-induced photo-damage in human skin fibroblasts

NASA Astrophysics Data System (ADS)

Lee, Kwon-Jai; An, Jeung-Hee; Shin, Jae-Soo; Kim, Dong-Hee; Kim, Changman; Ozaki, Hajime; Koh, Jae-Gui

2007-11-01

This study examined the optical properties of an oxidized form of maghemite (γ-Fe2O3) nanoparticles and their protective effects against the photoaging of human skin fibroblasts irradiated with ultraviolet (UV) light. Nanoparticles with diameters ranging from 8.7 to 12 nm were prepared using a chemical co-precipitation method. The nanoparticles were coated with two surfactants to obtain a water-based product. The onset of the absorption of the γ-Fe2O3 nanoparticles in the UV-visible absorption spectra increased with increasing particle size. The γ-Fe2O3 nanoparticles significantly inhibited the production of matrix metalloproteinase-1 in human skin fibroblast HS 68 cells by 60% compared with the UV-irradiated control. These results suggest that γ-Fe2O3 nanoparticles have photoprotective properties, and have potential use as an agent against photoaging.

Germacrone and sesquiterpene-enriched extracts from Curcuma aeruginosa Roxb. increase skin penetration of minoxidil, a hair growth promoter.

PubMed

Srivilai, Jukkarin; Waranuch, Neti; Tangsumranjit, Anothai; Khorana, Nantaka; Ingkaninan, Kornkanok

2018-02-01

Minoxidil is approved for topical treatment of androgenic alopecia but hampered by poor cutaneous absorption. Recently, the randomized control trial showed that hair loss treatment of minoxidil was improved by co-application of the anti-androgen, Curcuma aeruginosa Roxb. extract. Here, we aimed to show that the apparent synergism arises from improved cutaneous penetration of minoxidil by bioactive compound, germacrone or C. aeruginosa (as an n-hexane extract, or essential oil). The partition coefficient of germacrone was determined by HPLC. Skin penetration was measured ex vivo on Franz diffusion cells using full thickness human foreskin as membranes. The receiver solution was sampled hourly for 8 h after which the skin was removed, the stratum corneum separated, and minoxidil assayed in this and in the remaining viable skin layer by HPLC. Skin penetration of minoxidil with 0.2 and 2% extract was increased ~ 4-fold (accumulated amount in receiver + skin viable layer after 8 h). Furthermore, germacrone enhanced minoxidil flux by ~ 10-fold and C. aeruginosa essential oil by ~ 20-fold. This work suggests three clinical consequences: (i) minoxidil efficacy is promoted, (ii) lower doses of minoxidil suffice, and (iii) C. aeruginosa extract/essential oil or germacrone can supplement treatment outcomes by acting as anti-androgen, thereby introducing a more effective topical treatment strategy for androgenic alopecia.

Cell membrane penetration and mitochondrial targeting by platinum-decorated ceria nanoparticles

NASA Astrophysics Data System (ADS)

Torrano, Adriano A.; Herrmann, Rudolf; Strobel, Claudia; Rennhak, Markus; Engelke, Hanna; Reller, Armin; Hilger, Ingrid; Wixforth, Achim; Bräuchle, Christoph

2016-07-01

In this work we investigate the interaction between endothelial cells and nanoparticles emitted by catalytic converters. Although catalyst-derived particles are recognized as growing burden added to environmental pollution, very little is known about their health impact. We use platinum-decorated ceria nanoparticles as model compounds for the actual emitted particles and focus on their fast uptake and association with mitochondria, the cell's powerhouse. Using live-cell imaging and electron microscopy we clearly show that 46 nm platinum-decorated ceria nanoparticles can rapidly penetrate cell membranes and reach the cytosol. Moreover, if suitably targeted, these particles are able to selectively attach to mitochondria. These results are complemented by cytotoxicity assays, thus providing insights into the biological effects of these particles on cells. Interestingly, no permanent membrane disruption or any other significant adverse effects on cells were observed. The unusual uptake behavior observed for 46 nm nanoparticles was not observed for equivalent but larger 143 nm and 285 nm platinum-decorated particles. Our results demonstrate a remarkable particle size effect in which particles smaller than ~50-100 nm escape the usual endocytic pathway and translocate directly into the cytosol, while particles larger than ~150 nm are internalized by conventional endocytosis. Since the small particles are able to bypass endocytosis they could be explored as drug and gene delivery vehicles. Platinum-decorated nanoparticles are therefore highly interesting in the fields of nanotoxicology and nanomedicine.In this work we investigate the interaction between endothelial cells and nanoparticles emitted by catalytic converters. Although catalyst-derived particles are recognized as growing burden added to environmental pollution, very little is known about their health impact. We use platinum-decorated ceria nanoparticles as model compounds for the actual emitted particles and

Runaway Electrons Modeling and Nanoparticle Plasma Jet Penetration into Tokamak Plasma

NASA Astrophysics Data System (ADS)

Galkin, S. A.; Bogatu, I. N.

2017-10-01

A novel idea to probe runaway electrons (REs) by superfast injection of high velocity nanoparticle plasma jet (NPPJ) from a plasma accelerator needs to be sustained by both RE dynamics modeling and simulation of NPPJ penetration through increasing tokamak magnetic field. We present our recent progress in both areas. RE simulation is based on the model, including Dreicer and ``avalanche'' mechanisms of RE generation, with emphasis on high Zeff effects. The high-density hyper-velocity C60 and BN NPPJ penetration through transversal B-field is conducted with the Hybrid Electro-Magnetic code (HEM-2D) in cylindrical coordinates, with 1/R B-field dependence for both DIII-D and ITER tokamaks. Work is supported in part by US DOE SBIR Grant.

Skin penetration surrogate for the evaluation of less lethal kinetic energy munitions.

PubMed

Bir, Cynthia A; Resslar, Marianne; Stewart, Shelby

2012-07-10

Although the benefits of the use of less lethal kinetic energy munitions are numerous, there is a need to evaluate the munitions prior to deployment to ensure their intended effect. The objective of the current research was to validate a surrogate that could be used to predict the risk of penetration of these devices. Existing data from biomechanical testing with post-mortem human specimens (PMHS) served as the foundation for this research. Development of the surrogate involved simulating the various layers of the skin and underlying soft tissues using a combination of materials. A standardized 12-gauge impactor was used to assess each combination. The energy density that resulted in a 50% risk of penetration for the anterior thorax region (23.99 J/cm(2)) from the previous research was matched using a specific combination of layers. Twelve various combinations of materials were tested with the 50% risk of penetration determined. The final validated surrogate consisted of a Laceration Assessment Layer (LAL) of natural chamois and .6 cm of closed-cell foam over a Penetration Assessment Layer (PAL) of 20% ordnance gelatin. This surrogate predicted a 50% risk of penetration at 23.88 J/cm(2). Injury risk curves for the PMHS and surrogate development work are presented. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

tLyP-1-conjugated mesoporous silica nanoparticles for tumor targeting and penetrating hydrophobic drug delivery

NASA Astrophysics Data System (ADS)

Xu, Baiyao; Ju, Yang; Song, Guanbin; Cui, Yanbin

2013-12-01

Mesoporous silica nanoparticles (MSNs) are among the most appealing candidates for targeted drug delivery, a process for which it is essential that nanoparticles be internalized into targeted cells with high speed and efficiency. Therefore, it is necessary to conjugate a targeting ligand to the surface of a nanocarrier in order to trigger rapid receptor-mediated endocytosis and effective cellular uptake, which occurs following recognition and selective binding to a target cell's membrane receptor. Here, a tumor targeting and penetrating drug delivery system (DDS) based on MSNs ( 100 nm in size) is described. The MSNs were functionalized by engrafting with the tumor-homing and penetrating peptide tLyP-1. The fabricated MSN-tLyP-1 loaded with camptothecin (CPT) showed a robust targeting and penetrating efficiency to HeLa cells and MCF-7 cells and induced the death of these cells. Moreover, the adverse side effect of CPT on human mesenchymal stem cells (hMSCs) was minimized, because the nanoparticles were selectively targeted to the tumor cells, and little hydrophobic CPT was released into the culture medium or blood. The results indicate that the MSN-tLyP-1 DDS has great potential for the delivery of hydrophobic anticancer drugs to target tumors.

Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique.

PubMed

Martins, Rodrigo Molina; Siqueira, Silvia; Fonseca, Maria José Vieira; Freitas, Luis Alexandre Pedro

2014-01-01

Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen's photoprotection were impaired by the microencapsulation process. The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique. The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53-102.2%), average particle sizes between 28.5 and 60.0 µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation. The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.

Nano-formulation for topical treatment of precancerous lesions: skin penetration, in vitro, and in vivo toxicological evaluation.

PubMed

Calienni, Maria Natalia; Temprana, Carlos Facundo; Prieto, Maria Jimena; Paolino, Donatella; Fresta, Massimo; Tekinay, Ayse Begum; Alonso, Silvia Del Valle; Montanari, Jorge

2018-06-01

With the aim of improving the topical delivery of the antineoplastic drug 5-fluorouracil (5FU), it was loaded into ultradeformable liposomes composed of soy phosphatidylcholine and sodium cholate (UDL-5FU). The liposome populations had a mean size of 70 nm without significant changes in 56 days, and the ultradeformable formulations were up to 324-fold more elastic than conventional liposomes. The interaction between 5FU and the liposomal membrane was studied by three methods, and also release profile was obtained. UDL-5FU did penetrate the stratum corneum of human skin. At in vitro experiments, the formulation was more toxic on a human melanoma-derived than on a human keratinocyte-derived cell line. Cells captured liposomes by metabolically active processes. In vivo toxicity experiments were carried out in zebrafish (Danio rerio) larvae by studying the swimming activity, morphological changes, and alterations in the heart rate after incubation. UDL-5FU was more toxic than free 5FU. Therefore, this nano-formulation could be useful for topical application in deep skin precancerous lesions with advantages over current treatments. This is the first work that assessed the induction of apoptosis, skin penetration in a Saarbrücken penetration model, and the toxicological effects in vivo of an ultradeformable 5FU-loaded formulation.

New method to detect organic nanoparticles in live tissue

NASA Astrophysics Data System (ADS)

Fixler, Dror; Yariv, Inbar

2015-03-01

In recent years, infiltrating materials into the human body has become a great challenge many researches are facing. In medicine and cosmetics today, there are materials which are administrated to patients by injection only. The main challenge with topical medication is penetrating the skin barrier. The skin is an effective barrier between the body and the outside environment, which prevents foreign materials entering the body easily. However, reducing the size of the desired materials might help their skin penetration ability. Recently nanoparticles (NPs) are being evaluated for use in many fields like chemistry, biology, medicine, physics and optics. The technique used in this work for forming organic NPs (ONPs) is the application of sonic waves to an aqueous solution, known as sonochemistry. To investigate the physical penetration depth of ONPs into the human body, we first developed a novel optical technique for detecting NPs within tissues. The detection of NPs is done by the extraction and investigation of the reemitted light phase.

Skin protection efficacy from UV irradiation and skin penetration property of polysaccharide-benzophenone conjugates as a sunscreen agent.

PubMed

Heo, Sukyoung; Hwang, Hee Sook; Jeong, Yohan; Na, Kun

2018-09-01

Sunscreen materials have been developed to protect skin from UV radiation. However, many organic sunscreen materials are small molecules and absorbed into human skin after topical application and lead to systemic side effects. To improve the adverse effects of conventional sunscreen materials, we designed a sunscreen agent using an organic sunscreen material and a polymer. Dioxybenzone, an organic sunscreen compound is selected and polymerized with natural polymer pullulan. Polymerization not only provides a long polymer backbone to dioxybenzone, but also keeps the distance between benzene rings of the dioxybenzone and prevents reduction of photoabsorption intensity. UV/vis spectrophotometry confirmed that dioxybenzone-pullulan polymer (DOB-PUL) and dioxybenzone (DOB) demonstrated similar UV absorption. To measure the accumulation of sunscreen materials on skin, Franz diffusion cell was used to confirm the accumulation of DOB and lack of penetration of DOB-PUL. Most importantly, DOB showed higher plasma concentration after multiple applications compared to that of DOB-PUL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative behavior between sunscreens based on free or encapsulated UV filters in term of skin penetration, retention and photo-stability.

PubMed

Cozzi, Arianna C; Perugini, Paola; Gourion-Arsiquaud, Samuel

2018-06-03

The growing incidence of photodamaging effects caused by UV radiation (e.g. sunburn, skin cancer) has increased the attention from health authorities which recommend the topical application of sunscreens to prevent these skin damages. The economic stakes for those companies involved in this international market are to develop new UV filters and innovative technologies to provide the most efficient, flexible and robust sunscreen products. Today the development of innovative and competitive sunscreen products is a complex formulation challenge. Indeed, the current sunscreens must protect against skin damages, while also being safe for the skin and being sensory and visually pleasant for the customers when applied on the skin. Organic UV filters, while proposing great advantages, also present the risk to penetrate the stratum corneum and diffuse into underlying structures with unknown consequences; moreover, their photo-stability are noted thorny outcomes in sunscreen development and subsequent performance. In recent years, the evaluation of the interaction between skin and sunscreen in terms of penetration after topical application has been considered from European authority but still its testing as their photo-stability assessment are not mandatory in most countries. This study, based on in-vitro approaches, was performed to evaluate and compare the retention and the penetration of organic UV filters in free or encapsulated form inside the skin as well as their respective photo-stability. Sunscreen formulation with a combination of Avobenzone and Octocrylene in "free form" and a formulation using the same UV filters but encapsulated in a sol-gel silica capsule, were analyzed and compared by FTIR Imaging Spectroscopy. Tape stripping method was used to investigate the penetration of these UV filters inside the stratum corneum. Their photo-stabilities were evaluated by spectroscopic measurements (FTIR, UV/Vis) and standard measurements were calculated: AUC (Area Under

Partner-facilitating transmembrane penetration of nanoparticles: a biological test in silico.

PubMed

Wang, W; Yang, R; Zhang, F; Yuan, B; Yang, K; Ma, Y

2018-06-21

Transmembrane penetration of nanoparticles (NPs) promises an effective pathway for cargo delivery into cells, and offers the possibility of organelle-specific targeting for biomedical applications. However, a full understanding of the underlying NP-membrane interaction mechanism is still lacking. In this work, the membrane penetration behavior of NPs is statistically analyzed based on the simulations of over 2.2 ms, which are performed with dissipative particle dynamics (DPD). Influences from multiple factors including the NP concentration, shape and surface chemistry are taken into account. It is interesting to find that, the introduction of a partner NP would greatly facilitate the transmembrane penetration of a host spherical NP. This is probably due to the membrane-mediated cooperation between the NPs. Moreover, the proper selection of a partner NP with specific surface chemistry is of great significance. For example, the best partner for a hydrophilic NP to achieve transmembrane penetration is a Janus-like one, in comparison with the hydrophilic, hydrophobic or randomly surface-decorated NPs. Furthermore, such a partner-facilitating effect in NP translocation also works for a shaped NP although less pronounced. Our results are helpful for a better understanding of the complicated nano-bio interactions, and offer a practical guide to the NP-based drug delivery strategy with high efficiency.

Structure-skin permeability relationship of dendrimers.

PubMed

Venuganti, Venkata Vamsi; Sahdev, Preety; Hildreth, Michael; Guan, Xiangming; Perumal, Omathanu

2011-09-01

To investigate skin penetration of poly (amidoamine) (PAMAM) dendrimers as a function of surface charge and molecular weight in presence and absence of iontophoresis. Dendrimers were labeled with fluoroisothiocynate (FITC); skin penetration of dendrimers was studied using excised porcine skin in-vitro. Skin penetration of FITC-labeled dendrimers was quantified using confocal laser scanning microscope (CLSM). G2-G6 NH(2), G3.5-COOH and G4-OH dendrimers were used. Cationic dendrimers showed higher skin penetration than neutral and anionic dendrimers. Skin penetration of cationic dendrimer increased linearly with increase in treatment time. Iontophoresis enhanced skin penetration of cationic and neutral dendrimers. Increase in current strength and current duration increased skin transport of dendrimers. Passive and iontophoretic skin penetration of cationic dendrimers was inversely related to their molecular weight. Dendrimer penetrated the skin through intercellular lipids and hair follicles. With iontophoresis, dendrimer was also found in localized skin regions. The study demonstrates that the physicochemical properties of dendrimers influence their skin transport. Findings can be used to design dendrimer-based nanocarriers for drug delivery to skin.

Dermal uptake and percutaneous penetration of ten flame retardants in a human skin ex vivo model.

PubMed

Frederiksen, Marie; Vorkamp, Katrin; Jensen, Niels Martin; Sørensen, Jens Ahm; Knudsen, Lisbeth E; Sørensen, Lars S; Webster, Thomas F; Nielsen, Jesper B

2016-11-01

The dermal uptake and percutaneous penetration of ten organic flame retardants was measured using an ex vivo human skin model. The studied compounds were DBDPE, BTBPE, TBP-DBPE, EH-TBB, BEH-TEBP, α, β and γ-HBCDD as well as syn- and anti-DDC-CO. Little or none of the applied flame retardants was recovered in either type of the receptor fluids used (physiological and worst-case). However, significant fractions were recovered in the skin depot, particularly in the upper skin layers. The primary effect of the worst-case receptor fluid was deeper penetration into the skin. The recovered mass was used to calculate lower- and upper-bound permeability coefficients kp. Despite large structural variation between the studied compounds, a clear, significant decreasing trend of kp was observed with increasing log Kow. The results indicate that the dermis may provide a significant barrier for these highly lipophilic compounds. However, based on our results, dermal uptake should be considered in exposure assessments, though it may proceed in a time-lagged manner compared to less hydrophobic compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell-Penetrating Peptide-Modified Gold Nanoparticles for the Delivery of Doxorubicin to Brain Metastatic Breast Cancer.

PubMed

Morshed, Ramin A; Muroski, Megan E; Dai, Qing; Wegscheid, Michelle L; Auffinger, Brenda; Yu, Dou; Han, Yu; Zhang, Lingjiao; Wu, Meijing; Cheng, Yu; Lesniak, Maciej S

2016-06-06

As therapies continue to increase the lifespan of patients with breast cancer, the incidence of brain metastases has steadily increased, affecting a significant number of patients with metastatic disease. However, a major barrier toward treating these lesions is the inability of therapeutics to penetrate into the central nervous system and accumulate within intracranial tumor sites. In this study, we designed a cell-penetrating gold nanoparticle platform to increase drug delivery to brain metastatic breast cancer cells. TAT peptide-modified gold nanoparticles carrying doxorubicin led to improved cytotoxicity toward two brain metastatic breast cancer cell lines with a decrease in the IC50 of at least 80% compared to free drug. Intravenous administration of these particles led to extensive accumulation of particles throughout diffuse intracranial metastatic microsatellites with cleaved caspase-3 activity corresponding to tumor foci. Furthermore, intratumoral administration of these particles improved survival in an intracranial MDA-MB-231-Br xenograft mouse model. Our results demonstrate the promising application of gold nanoparticles for improving drug delivery in the context of brain metastatic breast cancer.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

NASA Astrophysics Data System (ADS)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Hyeok Choi, Byeong; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon; Son, Sang Wook

2011-07-01

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

PubMed Central

Palmer, Brian C.; DeLouise, Lisa A.

2017-01-01

Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

PubMed

Palmer, Brian C; DeLouise, Lisa A

2016-12-15

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

An animal study of a newly developed skin-penetrating pad and covering material for catheters to prevent exit-site infection in continuous ambulatory peritoneal dialysis.

PubMed

Aoyama, Masato; Mizuno, Toshihide; Tatsumi, Eisuke; Taenaka, Yoshiyuki; Nemoto, Yasushi; Okamoto, Yoshihiro; Takemoto, Yoshiaki; Naganuma, Toshihide; Nakatani, Tatsuya

2009-12-01

Because currently available peritoneal dialysis catheters are not sufficiently biocompatible with the skin and subcutaneous tissue at the site of penetration, exit-site infection due to pericatheter pocket formation caused by epidermal downgrowth over a long period of time has increasingly become a problem. We developed a new, biocompatible, segmented polyurethane porous material and devised a novel skin-penetrating pad, the form and material of which we optimized for application in peritoneal dialysis catheters. For the extent of tissue ingrowth into this porous material to be examined, test materials with different pore diameters were inserted into hollow silicone tubes and implanted in the subcutaneous tissue of a goat. Four weeks later, the tubes were extracted, and, after the extent of granulation tissue ingrowth was measured, histopathological evaluation was made. Our novel skin-penetrating pad has three disklike layers of the segmented polyurethane material with different pore sizes, into the center of which a polyurethane catheter is inserted. These pads were implanted in the skin of a goat and clinically observed over a 2-year period, after which they were extracted and histopathologically analyzed. In accordance with actual clinical procedures, a commercial CAPD catheter equipped with our skin-penetrating pad was left indwelling in a goat for 4 months, and the performance of the pad was evaluated after repeated periodic infusion and drainage of the dialysate in and out of the abdominal cavity. There was no inflammation of the ingrown tissue in the pores of the segmented polyurethane material as well as the surrounding tissue, which indicated favorable tissue biocompatibility. The extent of tissue ingrowth was greater as the pore size of the material was larger, and the tissue tended to be mature, mainly consisting of collagenous fibers. The skin-penetrating pad using the porous material, of which tissue ingrowth was thus optimized, tightly adhered to the

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

Effect of chitosan nanoparticle, QMix, and EDTA on TotalFill BC sealers' dentinal tubule penetration: a confocal laser scanning microscopy study.

PubMed

Aydın, Zeliha Uğur; Özyürek, Taha; Keskin, Büşra; Baran, Talat

2018-04-12

The aim of the present study was to compare the effect of chitosan nanoparticle, QMix, and 17% EDTA on the penetrability of a calcium silicate-based sealer into dentinal tubules using a confocal laser scanning microscope (CLSM). Sixty mandibular premolar teeth were selected and randomly divided into three groups (n = 20) before root canal preparation according to the solution used in the final rinse protocol: chitosan, QMix, and EDTA groups. Twenty teeth of each group were filled with a TotalFill BC sealers' single gutta-percha cone and with 0.1% rhodamine B. The specimens were horizontally sectioned at 3 and 5 mm from the apex, and the slices were analyzed in CLSM (4×). Total percentage and maximum depth of sealer penetration were measured using confocal laser scanning microscopy with using Image J analysis software. Dentinal tubule's penetration depth, percentage, and area were measured using imaging software. Kruskal-Wallis test was used for statistical analysis. The level of significance was set at 5%. Results of Kruskal-Wallis analysis showed that there was a significant difference in the percentage and depth of sealer penetration among all groups at 3 and 5 mm level sections (P < 0.05). Within the groups, the minimum sealer penetration depth was recorded for chitosan nanoparticle group. Greater depth of sealer penetration was recorded at 5 mm as compared to 3 mm in all the groups. Within the limitation of the present study, it can be concluded that QMix and EDTA promoted sealer penetration superior to that achieved by chitosan nanoparticle.

Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo.

PubMed

Mujica Ascencio, Saul; Choe, ChunSik; Meinke, Martina C; Müller, Rainer H; Maksimov, George V; Wigger-Alberti, Walter; Lademann, Juergen; Darvin, Maxim E

2016-07-01

Propylene glycol is one of the known substances added in cosmetic formulations as a penetration enhancer. Recently, nanocrystals have been employed also to increase the skin penetration of active components. Caffeine is a component with many applications and its penetration into the epidermis is controversially discussed in the literature. In the present study, the penetration ability of two components - caffeine nanocrystals and propylene glycol, applied topically on porcine ear skin in the form of a gel, was investigated ex vivo using two confocal Raman microscopes operated at different excitation wavelengths (785nm and 633nm). Several depth profiles were acquired in the fingerprint region and different spectral ranges, i.e., 526-600cm(-1) and 810-880cm(-1) were chosen for independent analysis of caffeine and propylene glycol penetration into the skin, respectively. Multivariate statistical methods such as principal component analysis (PCA) and linear discriminant analysis (LDA) combined with Student's t-test were employed to calculate the maximum penetration depths of each substance (caffeine and propylene glycol). The results show that propylene glycol penetrates significantly deeper than caffeine (20.7-22.0μm versus 12.3-13.0μm) without any penetration enhancement effect on caffeine. The results confirm that different substances, even if applied onto the skin as a mixture, can penetrate differently. The penetration depths of caffeine and propylene glycol obtained using two different confocal Raman microscopes are comparable showing that both types of microscopes are well suited for such investigations and that multivariate statistical PCA-LDA methods combined with Student's t-test are very useful for analyzing the penetration of different substances into the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Silver Nanoparticle Toxicity in Skin in Vivo and Keratinocytes in Vitro

PubMed Central

Samberg, Meghan E.; Oldenburg, Steven J.; Monteiro-Riviere, Nancy A.

2010-01-01

Introduction Products using the antimicrobial properties of silver nanoparticles (Ag-nps) may be found in health and consumer products that routinely contact skin. Objectives This study was designed to assess the potential cytotoxicity of Ag-nps in human epidermal keratinocytes (HEKs) and their inflammatory and penetrating potential into porcine skin in vivo. Materials and Methods We used eight different Ag-nps in this study [unwashed/uncoated (20, 50, and 80 nm particle diameter), washed/uncoated (20, 50, and 80 nm), and carbon-coated (25 and 35 nm)]. Skin was dosed topically for 14 consecutive days. HEK viability was assessed by MTT, alamarBlue (aB), and CellTiter 96 AQueous One (96AQ). Release of the proinflammatory mediators interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were measured. Results The effect of the unwashed Ag-nps on HEK viability after a 24-hr exposure indicated a significant dose-dependent decrease (p < 0.05) at 0.34 μg/mL with aB and 96AQ and at 1.7 μg/mL with MTT. However, both the washed Ag-nps and carbon-coated Ag-nps showed no significant decrease in viability at any concentration assessed by any of the three assays. For each of the unwashed Ag-nps, we noted a significant increase (p < 0.05) in IL-1β, IL-6, IL-8, and TNF-α concentrations. We observed localization of all Ag-nps in cytoplasmic vacuoles of HEKs. Macroscopic observations showed no gross irritation in porcine skin, whereas microscopic and ultrastructural observations showed areas of focal inflammation and localization of Ag-nps on the surface and in the upper stratum corneum layers of the skin. Conclusion This study provides a better understanding Ag-nps safety in vitro as well as in vivo and a basis for occupational and risk assessment. Ag-nps are nontoxic when dosed in washed Ag-nps solutions or carbon coated. PMID:20064793

Mucus-Penetrating Nanoparticles for Vaginal Drug Delivery Protect Against Herpes Simplex Virus

PubMed Central

Ensign, Laura M.; Tang, Benjamin C.; Wang, Ying-Ying; Tse, Terence A.; Hoen, Timothy; Cone, Richard; Hanes, Justin

2013-01-01

Incomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We investigated vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution. Moreover, when delivered hypotonically, MPPs were transported advectively (versus diffusively) through mucus deep into vaginal folds (rugae) within minutes. By penetrating into the deepest mucus layers, more MPPs were retained in the vaginal tract after 6 h compared to CPs. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then developed MPPs composed of acyclovir monophosphate (ACVp). When administered prior to vaginal herpes simplex virus 2 (HSV-2) challenge, ACVp-MPPs protected 53% of mice, compared to only 16% protected by soluble drug. Overall, MPPs improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week. PMID:22700955

Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers.

PubMed

Döge, Nadine; Hönzke, Stefan; Schumacher, Fabian; Balzus, Benjamin; Colombo, Miriam; Hadam, Sabrina; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Schäfer-Korting, Monika; Schindler, Anke; Rühl, Eckart; Skov, Per Stahl; Church, Martin K; Hedtrich, Sarah; Kleuser, Burkhard; Bodmeier, Roland; Vogt, Annika

2016-11-28

Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-term ex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for

In vitro penetration through the skin layers of topically applied glucocorticoids.

PubMed

Carrer, Victor; Alonso, Cristina; Oliver, Marc Adrià; Coderch, Luisa

2018-05-22

Corticoids are actives widely used in the treatment of skin diseases. This work aims to study the penetration of three corticoids (betamethasone, clobetasol and flurandrenolide), their relationship with their Log D values and the effects of the vehicles. The three compounds were applied on a Franz-type diffusion cell in propylene glycol solution and their respective commercial creams and ointments. The active amounts found in the stratum corneum, epidermal and dermal layers of the skin were investigated. Their diffusions were greatly affected by the formulation, moreover higher amounts of substance in the epidermis and dermis were detected in ointments than in creams. The enhancement effect of propylene glycol was also observed. Moreover, the differences between the three substances could be related to their lipophilicity, molecular structure and molecular weight. The more hydrophobic compounds (clobetasol and betamethasone) are present in higher amounts in the epidermis and dermis, while the hydrophilic compound (flurandrenolide) is mostly present in the receptor fluid. This article is protected by copyright. All rights reserved.

Anti-Melanogenic Potentials of Nanoparticles from Calli of Resveratrol-Enriched Rice against UVB-Induced Hyperpigmentation in Guinea Pig Skin.

PubMed

Lee, Taek Hwan; Kang, Ji Hee; Seo, Jae Ok; Baek, So-Hyeon; Moh, Sang Hyun; Chae, Jae Kyoung; Park, Yong Un; Ko, Young Tag; Kim, Sun Yeou

2016-01-01

We already reported that genetically engineered resveratrol-enriched rice (RR) showed to down-regulate skin melanogenesis. To be developed to increase the bioactivity of RR using calli from plants, RR was adopted for mass production using plant tissue culture technologies. In addition, high-pressure homogenization (HPH) was used to increase the biocompatibility and penetration of the calli from RR into the skin. We aimed to develop anti-melanogenic agents incorporating calli of RR (cRR) and nanoparticles by high-pressure homogenization, examining the synergistic effects on the inhibition of UVB-induced hyperpigmentation. Depigmentation was observed following topical application of micro-cRR, nano-calli of normal rice (cNR), and nano-cRR to ultraviolet B (UVB)-stimulated hyperpigmented guinea pig dorsal skin. Colorimetric analysis, tyrosinase immunostaining, and Fontana-Masson staining for UVB-promoted melanin were performed. Nano-cRR inhibited changes in the melanin color index caused by UVB-promoted hyperpigmentation, and demonstrated stronger anti-melanogenic potential than micro-cRR. In epidermal skin, nano-cRR repressed UVB-promoted melanin granules, thereby suppressing hyperpigmentation. The UVB-enhanced, highly expressed tyrosinase in the basal layer of the epidermis was inhibited by nano-cRR more prominently than by micro-cRR and nano-cNR. The anti-melanogenic potency of nano-cRR also depended on pH and particle size. Nano-cRR shows promising potential to regulate skin pigmentation following UVB exposure.

Molecular inclusion complex of curcumin-β-cyclodextrin nanoparticle to enhance curcumin skin permeability from hydrophilic matrix gel.

PubMed

Rachmawati, Heni; Edityaningrum, Citra Ariani; Mauludin, Rachmat

2013-12-01

Curcumin (CUR) has various pharmacological effects, but its extensive first-pass metabolism and short elimination half-life limit its bioavailability. Therefore, transdermal application has become a potential alternative to delivery CUR. To increase CUR solubility for the development of a transparent homogenous gel and also enhance the permeation rate of CUR into the skin, β-cyclodextrin-curcumin nanoparticle complex (BCD-CUR-N) was developed. CUR encapsulation efficiency was increased by raising the percentage of CUR to BCD up to 20%. The mean particle size of the best CUR loading formula was 156 nm. All evaluation data using infrared spectroscopy, Raman spectroscopy, powder X-ray diffractometry, differential thermal analysis and scanning electron microscopy confirmed the successful formation of the inclusion complex. BCD-CUR-N increased the CUR dissolution rate of 10-fold (p < 0.01). In addition, the improvement of CUR permeability acrossed skin model tissue was observed in gel containing the BCD-CUR-N and was about 1.8-fold when compared with the free CUR gel (p < 0.01). Overall, CUR in the form of the BCD-CUR-N improved the solubility further on the penetration of CUR.

Radiation dose enhancement in skin therapy with nanoparticle addition: A Monte Carlo study on kilovoltage photon and megavoltage electron beams

PubMed Central

Zheng, Xiao J; Chow, James C L

2017-01-01

AIM To investigated the dose enhancement due to the incorporation of nanoparticles in skin therapy using the kilovoltage (kV) photon and megavoltage (MV) electron beams. Monte Carlo simulations were used to predict the dose enhancement when different types and concentrations of nanoparticles were added to skin target layers of varying thickness. METHODS Clinical kV photon beams (105 and 220 kVp) and MV electron beams (4 and 6 MeV), produced by a Gulmay D3225 orthovoltage unit and a Varian 21 EX linear accelerator, were simulated using the EGSnrc Monte Carlo code. Doses at skin target layers with thicknesses ranging from 0.5 to 5 mm for the photon beams and 0.5 to 10 mm for the electron beams were determined. The skin target layer was added with the Au, Pt, I, Ag and Fe2O3 nanoparticles with concentrations ranging from 3 to 40 mg/mL. The dose enhancement ratio (DER), defined as the dose at the target layer with nanoparticle addition divided by the dose at the layer without nanoparticle addition, was calculated for each nanoparticle type, nanoparticle concentration and target layer thickness. RESULTS It was found that among all nanoparticles, Au had the highest DER (5.2-6.3) when irradiated with kV photon beams. Dependence of the DER on the target layer thickness was not significant for the 220 kVp photon beam but it was for 105 kVp beam for Au nanoparticle concentrations higher than 18 mg/mL. For other nanoparticles, the DER was dependent on the atomic number of the nanoparticle and energy spectrum of the photon beams. All nanoparticles showed an increase of DER with nanoparticle concentration during the photon beam irradiations regardless of thickness. For electron beams, the Au nanoparticles were found to have the highest DER (1.01-1.08) when the beam energy was equal to 4 MeV, but this was drastically lower than the DER values found using photon beams. The DER was also found affected by the depth of maximum dose of the electron beam and target thickness. For

Nanoparticles and spermatogenesis: how do nanoparticles affect spermatogenesis and penetrate the blood-testis barrier.

PubMed

Lan, Zhou; Yang, Wan-Xi

2012-04-01

Due to the widespread use of nanomaterials in medical, industrial and military applications, the question as to whether nanoparticles (NPs) cause harmful disturbances in human health, especially on the reproductive system, remains a matter of concern. In this review, we focus mainly on the in vivo and in vitro effects of NPs on spermatogenesis at the clinical, cellular and molecular levels. In general, most NPs display adverse effects on spermatogenesis at these various levels; but, some NPs show no adverse effects. However, the mechanism underlying NP disruption of spermatogenesis and penetration of the blood-testis barrier remains unclear. In this review, we raise many hypotheses for experimental testing in order to elucidate the mechanism.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations.

PubMed

Özcan, Ipek; Azizoğlu, Erkan; Senyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

PubMed Central

Özcan, İpek; Azizoğlu, Erkan; Şenyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders. PMID:23390364

Shaving effects on percutaneous penetration: clinical implications.

PubMed

Hamza, Muhammad; Tohid, Hassaan; Maibach, Howard

2015-01-01

Human/animal shaving biology. To assess the effect of shaving on percutaneous penetration and skin function. We screened 500+publications in Pub Med, Scopus, Cochrane Library and pertinent journals out of which only 17 were deemed relevant. Terms for searches included shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc. Shaving appears to have an exaggerated effect on percutaneous absorption; however, some studies do not support this evidence. Shaving enhances percutaneous penetration of some chemicals; however this effect is species and chemical specific. Further investigations of chemicals of varying physio-chemical properties are mandated before a generalized theory can be promulgated.

Hyaluronate nanoparticles included in polymer films for the prolonged release of vitamin E for the management of skin wounds.

PubMed

Pereira, Gabriela Garrastazu; Detoni, Cassia Britto; Balducci, Anna Giulia; Rondelli, Valeria; Colombo, Paolo; Guterres, Silvia Stanisçuaski; Sonvico, Fabio

2016-02-15

Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea.

PubMed

Chaiyasan, Wanachat; Praputbut, Sakonwun; Kompella, Uday B; Srinivas, Sangly P; Tiyaboonchai, Waree

2017-01-01

Topical application of drugs to the eyes suffers from poor bioavailability at the ocular surface and in the anterior chamber. This is due to rapid clearance of the drug because of tear secretion and outflow. This study has investigated mucoadhesive and penetration characteristics of chitosan-dextran sulfate nanoparticles (CDNs), prepared by polyelectrolyte complexation technique, following topical administration to the ocular surface. Topical FITC-labeled CDNs (FCDNs; mean size of 400nm and a surface charge of +48mV) were retained on the porcine ocular surface for more than 4h. Topical FCDNs were partially endocytosed into porcine corneal epithelial cells via a clathrin-dependent pathway. After 6h of topical FCDNs, particles accumulated in the corneal epithelium but not found in the corneal stroma. When epithelium was removed, FCDNs penetrated the stroma. Thus, CDNs are potentially useful for drug/gene delivery to the ocular surface and to stroma when epithelium is damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses.

PubMed

Chow, A T; Chen, A; Lattime, H; Morgan, N; Wong, F; Fowler, C; Williams, R R

2002-04-01

To probe the pharmacokinetic basis for the use of levofloxacin for complicated skin and skin-structure infections (SSSIs) at a once-daily dosage of 750 mg by investigating its penetration into skin tissue. Ten healthy volunteers were administered three oral, once-daily 750 mg doses of levofloxacin, and levofloxacin concentrations were subsequently measured over time (0.5-24 h) in skin-punch biopsy tissue and plasma. Skin tissue concentrations consistently exceeded those in plasma at every time point, with tissue/plasma ratios of 1.37 +/- 0.81 for peak concentration and 1.97 +/- 0.35 for area under the concentration versus time curve. Three of the ten subjects reported treatment-emergent adverse events (AEs) that were considered unrelated to treatment. An 11th subject who had enrolled in the study withdrew after AEs of mild severity that were possibly related to the study drug. The results support the clinical usage of levofloxacin 750 mg once-daily for complicated SSSIs.

Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging.

PubMed

Jiang, Jingying; Boese, Matthias; Turner, Paul; Wang, Ruikang K

2008-01-01

By use of a Fourier transform infrared (FTIR) spectroscopic imaging technique, we examine the dynamic optical clearing processes occurring in hyperosmotically biocompatible agents penetrating into skin tissue in vitro. The sequential collection of images in a time series provides an opportunity to assess penetration kinetics of dimethyl sulphoxide (DMSO) and glycerol beneath the surface of skin tissue over time. From 2-D IR spectroscopic images and 3-D false color diagrams, we show that glycerol takes at least 30 min to finally penetrate the layer of epidermis, while DMSO can be detected in epidermis after only 4 min of being topically applied over stratum corneum sides of porcine skin. The results demonstrate the potential of a FTIR spectroscopic imaging technique as an analytical tool for the study of dynamic optical clearing effects when the bio-tissue is impregnated by hyperosmotically biocompatible agents such as glycerol and DMSO.

Oral nanotherapeutics: Redox nanoparticles attenuate ultraviolet B radiation-induced skin inflammatory disorders in Kud:Hr- hairless mice.

PubMed

Feliciano, Chitho P; Nagasaki, Yukio

2017-10-01

The active participation of an anti-inflammatory drug in the biological pathways of inflammation is crucial for the achievement of beneficial and therapeutic effects. This study demonstrated the development of redox nanoparticles that can circulate in the blood at significantly high levels, thus increasing their efficacy as an oral treatment against the deleterious effects of reactive oxygen species (ROS) in an in vivo inflammatory skin model. To confirm the blood bioavailability of the nanoparticles, mice were injected with the nanoparticles solution (RNP N ) via oral gavage. Using electron spin resonance and radioactive labeling techniques, the blood circulation of the redox polymer that forms the nanoparticles was confirmed 24 h after oral administration. This contrasted with its low molecular weight counterpart (NH 2 -TEMPO), which peaked 15 min post injection and was found to be cleared rapidly within minutes after the peak. We then tested its efficacy in the inflammatory skin model. Kud:Hr-hairless mice were irradiated with UVB (302 nm) to induce skin damage and inflammation. Throughout the entire period of UVB irradiation, RNP N was administered to mice by free drinking. NH 2 -TEMPO was used as the control. The results showed that oral supplementation of RNP N significantly improved the therapeutic effects of the core nitroxide radical compared with its low molecular weight counterpart. Furthermore, RNP N significantly reduced UVB-induced skin aging, epidermal thickening, edema, erythema, skin lesions, and various pathological skin inflammatory disorders in vivo. From the obtained data, we concluded that the use of long-circulating redox nanoparticles (RNP N ) provided an effective treatment against the damaging effects of excessive ROS in the body. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electric Stimulus Opens Intercellular Spaces in Skin*

PubMed Central

Hama, Susumu; Kimura, Yuki; Mikami, Aya; Shiota, Kanako; Toyoda, Mao; Tamura, Atsushi; Nagasaki, Yukio; Kanamura, Kiyoshi; Kajimoto, Kazuaki; Kogure, Kentaro

2014-01-01

Iontophoresis is a technology for transdermal delivery of ionic small medicines by faint electricity. Since iontophoresis can noninvasively deliver charged molecules into the skin, this technology could be a useful administration method that may enhance patient comfort. Previously, we succeeded in the transdermal penetration of positively charged liposomes (diameters: 200–400 nm) encapsulating insulin by iontophoresis (Kajimoto, K., Yamamoto, M., Watanabe, M., Kigasawa, K., Kanamura, K., Harashima, H., and Kogure, K. (2011) Int. J. Pharm. 403, 57–65). However, the mechanism by which these liposomes penetrated the skin was difficult to define based on general knowledge of principles such as electro-repulsion and electro-osmosis. In the present study, we confirmed that rigid nanoparticles could penetrate into the epidermis by iontophoresis. We further found that levels of the gap junction protein connexin 43 protein significantly decreased after faint electric stimulus (ES) treatment, although occludin, CLD-4, and ZO-1 levels were unchanged. Moreover, connexin 43 phosphorylation and filamentous actin depolymerization in vivo and in vitro were observed when permeation of charged liposomes through intercellular spaces was induced by ES. Ca2+ inflow into cells was promoted by ES with charged liposomes, while a protein kinase C inhibitor prevented ES-induced permeation of macromolecules. Consequently, we demonstrate that ES treatment with charged liposomes induced dissociation of intercellular junctions via cell signaling pathways. These findings suggest that ES could be used to regulate skin physiology. PMID:24318878

Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review.

PubMed

Saez, V; Souza, I D L; Mansur, C R E

2018-04-01

The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Study of magnetic silk fibroin nanoparticles for massage-like transdermal drug delivery

PubMed Central

Chen, Ai-Zheng; Chen, Lin-Qing; Wang, Shi-Bin; Wang, Ya-Qiong; Zha, Jun-Zhe

2015-01-01

A synergistic approach by the combination of magnetic nanoparticles with an alternating magnetic field for transdermal drug delivery was investigated. Methotrexate-loaded silk fibroin magnetic nanoparticles were prepared using suspension-enhanced dispersion by supercritical CO2. The physiochemical properties of the magnetic nanoparticles were characterized. In vitro studies on drug permeation across skin were performed under different magnetic fields in comparison with passive diffusion. The permeation flux enhancement factor was found to increase under a stationary magnetic field, while an alternating magnetic field enhanced drug permeation more effectively; the combination of stationary and alternating magnetic fields, which has a massage-like effect on the skin, achieved the best result. The mechanistic studies using attenuated total reflection Fourier-transform infrared spectroscopy demonstrate that an alternating magnetic field can change the ordered structure of the stratum corneum lipid bilayers from the gel to the lipid-crystalline state, which can increase the fluidity of the stratum corneum lipids, thus enhancing skin penetration. Compared with the other groups, the fluorescence signal with a bigger area detected in deeper regions of the skin also reveals that the simulated massage could enhance the drug permeation across the skin by increasing the follicular transport. The combination of magnetic nanoparticles with stationary/alternating magnetic fields has potential for effective massage-like transdermal drug delivery. PMID:26229467

Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study

PubMed Central

Nivsarkar, Manish; Patel, Ketan R.; Patel, Dixit D.

2015-01-01

Introduction Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. Aim This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS® with diclofenac emulgel. Materials and Methods A 200 mg of diclofenac from either Dynapar QPS® (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Results Mean Cmax after administration of Dynapar QPS® and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0–t and AUC0-∞ after administration of Dynapar QPS® was higher as compared to diclofenac emulgel (AUC0–t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. Conclusion The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS® as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients. PMID:26816910

Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study.

PubMed

Nivsarkar, Manish; Maroo, Sanjaykumar H; Patel, Ketan R; Patel, Dixit D

2015-12-01

Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS(®) with diclofenac emulgel. A 200 mg of diclofenac from either Dynapar QPS(®) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Mean Cmax after administration of Dynapar QPS(®) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-∞ after administration of Dynapar QPS(®) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS(®) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients.

Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone?

PubMed

Cross, S E; Jiang, R; Benson, H A; Roberts, M S

2001-07-01

The effect of adding thickening agents on the penetration of a sunscreen benzophenone-3 through epidermal and a high-density polyethylene membrane was studied using both very thick (infinite dose) and thin (in use) applications. Contradictory results were obtained. Thickening agents retard skin penetration, in a manner consistent with a diffusional resistance in the formulation, when applied as an infinite dose. In contrast, when applied as in thin (in use) doses, thickening agents promote penetration, most likely through greater stratum corneum diffusivity arising from an enhanced hydration by the thicker formulations. The two key implications from this work are (i) a recognition of the danger in the potential extrapolation of infinite dosing to in use situations, and (ii) to recognize that thicker formulations may sometimes enhance the penetration of other topical agents when applied "in use".

Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer.

PubMed

Geetha, T; Kapila, Meenakshi; Prakash, Om; Deol, Parneet Kaur; Kakkar, Vandita; Kaur, Indu Pal

2015-02-01

Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines.

PubMed

Bhatnagar, Sunali; Kwan, James J; Shah, Apurva R; Coussios, Constantin-C; Carlisle, Robert C

2016-09-28

Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to 'self-propel'. In vivo murine studies indicated that nanocup-assisted ultrasound transdermal vaccination achieved significantly (p<0.05) higher delivery doses without visible skin damage compared to the use of a chemical penetration enhancer. Transdermal OVA doses of up to 1μg were achieved in a single 90-second treatment, which was sufficient to trigger an antigen-specific immune response. Furthermore, ultrasound-assisted vaccine delivery in the presence of nanocups demonstrated substantially higher specific anti-OVA IgG antibody levels compared to other transdermal methods. Further optimisation can lead to a viable, safe and non-invasive delivery platform for vaccines with potential use in a primary care setting or personalized self-vaccination at home. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Analysis and measurements of low frequency lightning component penetration through aerospace vehicle metal and graphite skins

NASA Technical Reports Server (NTRS)

Robb, J. D.; Chen, T.

1980-01-01

An analysis of the shielding properties of mixed metal and graphite composite structures has illustrated some important aspects of electromagnetic field penetration into the interior. These include: (1) that graphite access doors on metallic structures will attenuate lightning magnetic fields very little; conversely, metal doors on a graphite structure will also attenuate fields from lightning strike currents very little, i.e., homogeneity of the shield is a critical factor in shielding and (2) that continuous conductors between two points inside a graphite skin such as an air data probe metallic tubing connection to an air data computer can allow large current penetrations into a vehicle interior. The true weight savings resulting from the use of composite materials can only be evaluated after the resulting electromagnetic problems such as current penetrations have been solved, and this generally requires weight addition in the form of cable shields, conductor bonding or external metallization.

Development and Evaluation of Lipid Nanoparticles Containing Natural Botanical Oil for Sun Protection: Characterization and in vitro and in vivo Human Skin Permeation and Toxicity.

PubMed

Andréo-Filho, Newton; Bim, Antonio Vinicius Kosiski; Kaneko, Telma Mary; Kitice, Nidia Ayumi; Haridass, Isha N; Abd, Eman; Santos Lopes, Patricia; Thakur, Sachin S; Parekh, Harendra S; Roberts, Michael S; Grice, Jeffrey E; Benson, Heather A E; Leite-Silva, Vânia Rodrigues

2018-01-01

The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use. © 2017 S. Karger AG, Basel.

Current Challenges and Future of Lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye.

PubMed

Guilherme, Viviane A; Ribeiro, Ligia N M; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Paula, Eneida; de Jesus, Marcelo Bispo

2017-11-21

Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin and eye. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Noninvasive delivery of stealth, brain-penetrating nanoparticles across the blood-brain barrier using MRI-guided focused ultrasound

PubMed Central

Miller, G. Wilson; Song, Ji; Louttit, Cameron; Klibanov, Alexander L; Shih, Ting-Yu; Swaminathan, Ganesh; Tamargo, Rafael J.; Woodworth, Graeme F.; Hanes, Justin; Price, Richard J.

2014-01-01

The blood-brain barrier (BBB) presents a significant obstacle for the treatment of many central nervous system (CNS) disorders, including invasive brain tumors, Alzheimer’s, Parkinson’s and stroke. Therapeutics must be capable of bypassing the BBB and also penetrate the brain parenchyma to achieve a desired effect within the brain. In this study, we test the unique combination of a noninvasive approach to BBB permeabilization with a therapeutically relevant polymeric nanoparticle platform capable of rapidly penetrating within the brain microenvironment. MR-guided focused ultrasound (FUS) with intravascular microbubbles (MBs) is able to locally and reversibly disrupt the BBB with submillimeter spatial accuracy. Densely poly(ethylene-co-glycol) (PEG) coated, brain-penetrating nanoparticles (BPNs) are long-circulating and diffuse 10-fold slower in normal rat brain tissue compared to diffusion in water. Following intravenous administration of model and biodegradable BPN in normal healthy rats, we demonstrate safe, pressure-dependent delivery of 60 nm BPNs to the brain parenchyma in regions where the BBB is disrupted by FUS and MBs. Delivery of BPNs with MR-guided FUS has the potential to improve efficacy of treatments for many CNS diseases, while reducing systemic side effects by providing sustained, well-dispersed drug delivery into select regions of the brain. PMID:24979210

Skin penetration and antioxidant effect of cosmeto-textiles with gallic acid.

PubMed

Alonso, C; Martí, M; Barba, C; Lis, M; Rubio, L; Coderch, L

2016-03-01

In this work, the antioxidant gallic acid (GA) has been encapsulated in microspheres prepared with poly-ε-caprolactone (PCL) and incorporated into polyamide (PA) obtaining the cosmeto-textile. The topical application of the cosmeto-textile provides a reservoir effect in the skin delivery of GA. The close contact of the cosmeto-textile, containing microsphere-encapsulated GA (ME-GA), with the skin and their corresponding occlusion, may be the main reasons that explain the crossing of active principle (GA) through the skin barrier, located in the stratum corneum, and its penetration into the different compartments of the skin, epidermis and dermis. An ex vivo assessment was performed to evaluate the antioxidant effect of the ME-GA on the stratum corneum (SC) using the thiobarbituric acid-reactive species (TBARS) test. The test is based on a non-invasive ex vivo methodology that evaluates lipid peroxides formed in the outermost layers of the SC from human volunteers after UV radiation to determine the effectiveness of an antioxidant. In this case, a ME-GA cosmeto-textile or ME-GA formulation were applied to the skin in vivo and lipid peroxidation (LPO) in the horny layer were determined after UV irradiation. This methodology may be used as a quality control tool to determine ex vivo the percentage of LPO inhibition on human SC for a variety of antioxidants that are topically applied, in this case GA. Results show that LPO formation was inhibited in human SC when GA was applied directly or embedded in the cosmeto-textile, demonstrating the effectiveness of both applications. The percentage of LPO inhibition obtained after both topical applications was approximately 10% for the cosmeto-textile and 41% for the direct application of microspheres containing GA. This methodology could be used to determine the effectiveness of topically applied antioxidants encapsulated in cosmeto-textiles on human SC. Copyright © 2016 Elsevier B.V. All rights reserved.

Glabridin nanosuspension for enhanced skin penetration: formulation optimization, in vitro and in vivo evaluation.

PubMed

Wang, W P; Hul, J; Sui, H; Zhao, Y S; Feng, J; Liu, C

2016-05-01

Glabridin, a polyphenolic flavonoid from licorice, has inspired great interest for its antioxidant, anti-inflammatory and skin-lightening activities. However, low water solubility and poor stability of glabridin impedes its topical application in cosmetic products and therapies of dermal diseases. The purpose of this study was to develop a nanosuspension formulation of glabridin to improve its skin permeation. Glabridin nanosuspensions were prepared using anti-solvent precipitation-homogenization method, and Box-Behnken design was adopted to investigate the effects of crucial formulation variables on particle size and to optimize the nanosuspension formulation. The optimal formulation consisted of 0.25% glabridin, 0.47% Poloxamer 188 and 0.11% Polyvinylpyrrolidone K30, and the obtained nanosuspension showed an average particle size of 149.2 nm with a polydispersity index of 0.254. Furthermore, the nanosuspension exhibited significantly enhanced drug permeation flux of glabridin through rat skin with no lag phase both in vitro and in vivo, compared to the coarse suspension and physical mixture. The glabridin nanosuspension showed no significant particle aggregates and a drug loss of 5.46% after storage for 3 months at room temperature. With its enhanced skin penetration, the nanosuspension might be a more preferable formulation for topical administration of poorly soluble glabridin.

Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances.

PubMed

Savić, Vedrana; Todosijević, Marija; Ilić, Tanja; Lukić, Milica; Mitsou, Evgenia; Papadimitriou, Vassiliki; Avramiotis, Spyridon; Marković, Bojan; Cekić, Nebojša; Savić, Snežana

2017-08-30

In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy. Moreover, stability studies proved no change in tacrolimus content during one year of storage at room temperature. In addition, in vivo skin performance indicated no skin irritation potential of blank microemulsions, whereas in vitro release testing using Franz diffusion cells showed superior release rate of tacrolimus from microemulsions (0.98±0.10 and 0.92±0.11μg/cm 2 /h for two bicontinuous and 1.00±0.24μg/cm 2 /h for oil-in-water microemulsion) compared to referent Protopic ointment (0.15±0.08μg/cm 2 /h). Furthermore, ex vivo penetration assessed through porcine ear skin using tape stripping, confirmed superiority of two microemulsions related to the reference, implying developed microemulsions as promising carriers for dermal delivery of tacrolimus. Copyright © 2017 Elsevier B.V. All rights reserved.

Photoacoustic study of the penetration kinetics of nimesulid into human skin

NASA Astrophysics Data System (ADS)

Barja, P. R.; Veloso, D. J. D. V.

2010-03-01

The photoacoustic (PA) effect is observed when modulated (or pulsed) light is absorbed by a sample inside a closed chamber and converted in heat, generating acoustic waves; PA measurements have been employed to evaluate transdermal penetration of topically applied drugs. Phonophoresis is the utilization of ultrasonic (US) energy to enhance absorption of drugs across the epidermal barrier, and its usefulness has been shown by PA measurements. The aim of the present work was to determine the characteristic absorption times of the anti-inflammatory Nimesulid (gel) in human skin, with and without help of therapeutic phonophoresis. After local cleaning, measurements were performed in the forearm of each volunteer before Nimesulid application and for different times after application through massage with the US equipment head; the protocol was repeated for the opposite forearm, but without US emission. Curves of the PA signal level as a function of time were adjusted by a Boltzmann equation, leading to the determination of the characteristic absorption time (about 12 minutes). No significant gain was observed in Nimesulid absorption with the utilization of US radiation, indicating that topic application of Nimesulid does not require the use of phonophoresis, due to the natural fast penetration of the Nimesulid gel.

Application of aluminum phthalocyanine nanoparticles for fluorescent diagnostics in dentistry and skin autotransplantology.

PubMed

Vasilchenko, Sergey Yu; Volkova, Anna I; Ryabova, Anastasiya V; Loschenov, Victor B; Konov, Vitaly I; Mamedov, Adil A; Kuzmin, Sergey G; Lukyanets, Evgeniy A

2010-06-01

This paper deals with the possibility of application of aluminum phthalocyanine (AlPc) nanoparticles in clinical practice. AlPc fluoresces in the molecular form but in the form of nanoparticles it does not. Separation of molecules from an AlPc nanoparticle and therefore the appearance of fluorescence occurs under the effect of a number of biochemo-physical factors. Owing to this feature the application of AlPc nanoparticles followed by the measurement of fluorescence spectra is proposed as a diagnostics method. It was shown that after AlPc nanoparticle application on a tooth surface the fluorescence intensity in the enamel microdamage area is 2-3 times higher than that in the normal enamel area. The appearance of fluorescence after application of AlPc nanoparticles on skin autografts testifies to the presence of inflammation. (c) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gold Nanoparticles Cytotoxicity

NASA Astrophysics Data System (ADS)

Mironava, Tatsiana

Over the last two decades gold nanoparticles (AuNPs) have been used for many scientific applications and have attracted attention due to the specific chemical, electronic and optical size dependent properties that make them very promising agents in many fields such as medicine, imagine techniques and electronics. More specifically, biocompatible gold nanoparticles have a huge potential for use as the contrast augmentation agent in X-ray Computed Tomography and Photo Acoustic Tomography for early tumor diagnostic as well these nanoparticles are extensively researched for enhancing the targeted cancer treatment effectiveness such as photo-thermal and radiotherapy. In most biomedical applications biocompatible gold nanoparticles are labeled with specific tumor or other pathology targeting antibodies and used for site specific drug delivery. However, even though gold nanoparticles poses very high level of anti cancer properties, the question of their cytotoxicity ones they are released in normal tissue has to be researched. Moreover, the huge amount of industrially produced gold nanoparticles raises the question of these particles being a health hazard, since the penetration is fairly easy for the "nano" size substances. This study focuses on the effect of AuNPs on a human skin tissue, since it is fall in both categories -- the side effects for biomedical applications and industrial workers and users' exposure during production and handling. Therefore, in the present project, gold nanoparticles stabilized with the biocompatible agent citric acid were generated and characterized by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The cytotoxic effect of AuNPs release to healthy skin tissue was modeled on 3 different cell types: human keratinocytes, human dermal fibroblasts, and human adipose derived stromal (ADS) cells. The AuNPs localization inside the cell was found to be cell type dependent. Overall cytotoxicity was found to be dependent

Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro.

PubMed

Cross, Sheree E; Russell, Michael; Southwell, Ian; Roberts, Michael S

2008-05-01

The safety of topical application of Australian tea tree Oil (TTO) is confounded by a lack of transdermal penetration data, which adequately informs opinions and recommendations. In this study we applied TTO in its pure form and as a 20% solution in ethanol in vitro to human epidermal membranes from three different donors, mounted in horizontal Franz-type diffusion cells, using normal 'in use' dosing conditions (10 mg/cm2). In addition, we examined the effect of partially occluding the application site on the penetration of TTO components. Our data showed that only a small quantity of TTO components, 1.1-1.9% and 2-4% of the applied amount following application of a 20% TTO solution and pure TTO, respectively, penetrated into or through human epidermis. The largest TTO component penetrating the skin was terpinen-4-ol. Following partial occlusion of the application site, the penetration of terpinen-4-ol increased to approximately 7% of the applied TTO. Measurement of the rate of evaporation of tea tree oil from filter paper (7.4 mg/cm2) showed that 98% of the oil evaporated in 4 hours. Overall, it is apparent that the penetration of TTO components through human skin is limited.

Quantification of Cell-Penetrating Peptide Associated with Polymeric Nanoparticles Using Isobaric-Tagging and MALDI-TOF MS/MS

NASA Astrophysics Data System (ADS)

Chiu, Jasper Z. S.; Tucker, Ian G.; McDowell, Arlene

2016-11-01

High sensitivity quantification of the putative cell-penetrating peptide di-arginine-histidine (RRH) associated with poly (ethyl-cyanoacrylate) (PECA) nanoparticles was achieved without analyte separation, using a novel application of isobaric-tagging and high matrix-assisted laser desorption/ionization coupled to time-of-flight (MALDI-TOF) mass spectrometry. Isobaric-tagging reaction equilibrium was reached after 5 min, with 90% or greater RRH peptide successfully isobaric-tagged after 60 min. The accuracy was greater than 90%, which indicates good reliability of using isobaric-tagged RRH as an internal standard for RRH quantification. The sample intra- and inter-spot coefficients of variations were less than 11%, which indicate good repeatability. The majority of RRH peptides in the nanoparticle formulation were physically associated with the nanoparticles (46.6%), whereas only a small fraction remained unassociated (13.7%). The unrecovered RRH peptide (~40%) was assumed to be covalently associated with PECA nanoparticles.

Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.

PubMed

Zhu, Rui; Gao, Feng; Piao, Ji-Gang; Yang, Lihua

2017-07-25

How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm -2 ), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.

Lipid vesicles and other colloids as drug carriers on the skin.

PubMed

Cevc, Gregor

2004-03-27

Colloids from an aqueous suspension can cross the skin barrier only through hydrophilic pathways. Various colloids have a different ability to do this by penetrating narrow pores of fixed size in the skin, or the relevant nano-pores in barriers modelling the skin. Such ability is governed by colloid adaptability, which must be high enough to allow penetrant deformation to the size of a pore in such barrier: for a 100 nm colloid trespassing the skin this means at least 5-fold deformation/elongation. (Lipid) Bilayer vesicles are normally more adaptable than the comparably large (lipid coated) fluid droplets. One of the reasons for this, and an essential condition for achieving a high bilayer adaptability and pore penetration, is a high bilayer membrane elasticity. The other reason is the relaxation of changing colloid's volume-to-surface constraint during pore penetration; it stands to reason that such relaxation requires a concurrent, but only transient and local, bilayer permeabilisation. Both these phenomena are reflected in bilayer composition sensitivity, which implies non-linear pressure dependency of the apparent barrier penetrability, for example. Amphipats that acceptably weaken a membrane (surfactants, (co)solvents, such as certain alcohols, etc.) consequently facilitate controlled, local bilayer destabilisation and increase lipid bilayer flexibility. When used in the right quantity, such additives thus lower the energetic expense for elastic bilayer deformation, associated with pore penetration. Another prerequisite for aggregate transport through the skin is the colloid-induced opening of the originally very narrow ( approximately 0.4 nm) gaps between cells in the barrier to pores with diameter above 30 nm. Colloids incapable of enforcing such widening-and simultaneously of self-adapting to the size of 20-30 nm without destruction-are confined to the skin surface. All relatively compact colloids seem to fall in this latter category. This includes mixed

SU-F-T-361: Dose Enhancement Due to Nanoparticle Addition in Skin Radiotherapy: A Monte Carlo Study Using Kilovoltage Photon Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, X; Chow, J

Purpose: This study investigated the dose enhancement due to addition of nanoparticles with different types and concentrations in skin radiotherapy using kilovoltage photon beams. Methods: An inhomogeneous water phantom (15×15×10 cm{sup 3}) having the skin target layer (0.5–5 mm), added with different concentrations (3–40 mg/ml) of nanoparticles (Au, Pt, I, Ag and Fe{sub 2}O{sub 3}), was irradiated by the 105 and 220 kVp photon beams produced by a Gulmay D3225 Orthovoltage unit. The circular cone of 5-cm diameter and source-to-surface distance of 20 cm were used. Doses in the skin target layer with and without adding the nanoparticles were calculatedmore » using Monte Carlo simulation (the EGSnrc code) through the macroscopic approach. Dose enhancement ratio (DER), defined as the ratio of dose at the target with nanoparticle addition to the dose without addition, was calculated for each type and concentration of nanoparticle in different target thickness. Results: For Au nanoparticle, DER dependence on target thickness for the 220 kVp photon beams was not significant. However, DER for Au nanoparticle was found decreasing with an increase of target thickness when the nanoparticle concentration was increased from 18 to 40 mg/ml using the 105 kVp photon beams. For nanoparticle concentration of 40 mg/ml, DER variation with target thickness was not significant for the 220 kVp photon beams, but DEF was found decreasing with the target thickness when lower energy of photon beam (105 kVp) was used. DEF was found increasing with an increase of nanoparticle concentration. The higher the DEF increasing rate, the higher the atomic number of the nanoparticle except I and Ag for the same target thickness. Conclusion: It is concluded that nanoparticle addition can result in dose enhancement in kilovoltage skin radiotherapy. Moreover, the DER is related to the photon beam energy, target thickness, atomic number and concentration of nanoparticles.« less

The potent antimicrobial properties of cell penetrating peptide-conjugated silver nanoparticles with excellent selectivity for gram-positive bacteria over erythrocytes.

PubMed

Liu, Lihong; Yang, Jun; Xie, Jianping; Luo, Zhentao; Jiang, Jiang; Yang, Yi Yan; Liu, Shaomin

2013-05-07

Silver nanoparticles are of great interest for use as antimicrobial agents. Studies aimed at producing potent nano-silver biocides have focused on manipulation of particle size, shape, composition and surface charge. Here, we report the cell penetrating peptide catalyzed formation of antimicrobial silver nanoparticles in N,N-dimethylformamide. The novel nano-composite demonstrated a distinctly enhanced biocidal effect toward bacteria (gram-positive Bacillus subtilis, gram-negative Escherichia coli) and pathogenic yeast (Candida albicans), as compared to triangular and extremely small silver nanoparticles. In addition, a satisfactory biocompatibility was verified by a haemolysis test. Our results provide a paradigm in developing strategies that can maximize the silver nanoparticle application potentials while minimizing the toxic effects.

Combination Ointment Containing Solid Tranilast Nanoparticles and Dissolved Sericin Is Efficacious for Treating Skin Wound-Healing Deficits and Redness in Diabetic Rats.

PubMed

Nagai, Noriaki; Ogata, Fumihiko; Deguchi, Saori; Ueno, Akina; Kawasaki, Naohito; Ito, Yoshimasa

2017-01-01

We attempted to design a combination ointment containing solid tranilast nanoparticles and dissolved sericin as a wound-healing drug (TS-combination ointment), and evaluated its usefulness as therapy for wound-healing deficits in streptozotocin-induced diabetic rat (STZ rat) using kinetic analyses as an index. Solid tranilast nanoparticles were prepared by bead mill methods with low-substituted methylcellulose; the mean particle size of the tranilast nanoparticles was 70 nm. The ointment was designed to contain the tranilast nanoparticles plus sericin powder and/or Carbopol ® 934. Skin wound healing in STZ rats begins significantly later than in normal rats. Although the skin wound healing rate in STZ rats treated with an ointment containing tranilast nanoparticles was lower than in STZ rats treated with vehicle, the ointment was effective in reducing redness. An ointment containing sericin enhanced the skin-healing rate, but the preventive effect on redness was weak. On the other hand, the combination of tranilast and sericin increased both the skin healing rate and reduction in redness. In conclusion, we have adapted kinetic analyses to skin wound healing in rats, and found these analyses to be useful as an index of wound healing ability by a wound-healing drug. In addition, we show that treatment with the TS-combination ointment enhances the skin wound healing rate and reduces redness. These findings provide information significant to the search for new wound-healing therapies and for the design of wound-healing drugs.

Production of dissolvable microneedles using an atomised spray process: effect of microneedle composition on skin penetration.

PubMed

McGrath, Marie G; Vucen, Sonja; Vrdoljak, Anto; Kelly, Adam; O'Mahony, Conor; Crean, Abina M; Moore, Anne

2014-02-01

Dissolvable microneedles offer an attractive delivery system for transdermal drug and vaccine delivery. They are most commonly formed by filling a microneedle mold with liquid formulation using vacuum or centrifugation to overcome the constraints of surface tension and solution viscosity. Here, we demonstrate a novel microneedle fabrication method employing an atomised spray technique that minimises the effects of the liquid surface tension and viscosity when filling molds. This spray method was successfully used to fabricate dissolvable microneedles (DMN) from a wide range of sugars (trehalose, fructose and raffinose) and polymeric materials (polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose, hydroxypropylmethylcellulose and sodium alginate). Fabrication by spraying produced microneedles with amorphous content using single sugar compositions. These microneedles displayed sharp tips and had complete fidelity to the master silicon template. Using a method to quantify the consistency of DMN penetration into different skin layers, we demonstrate that the material of construction significantly influenced the extent of skin penetration. We demonstrate that this spraying method can be adapted to produce novel laminate-layered as well as horizontally-layered DMN arrays. To our knowledge, this is the first report documenting the use of an atomising spray, at ambient, mild processing conditions, to create dissolvable microneedle arrays that can possess novel, laminate layering. Copyright © 2013 Elsevier B.V. All rights reserved.

A Physical Mechanism to Explain the Delivery of Chemical Penetration Enhancers into Skin during Transdermal Sonophoresis - Insight into the Observed Synergism

PubMed Central

Polat, Baris E.; Deen, William M.; Langer, Robert; Blankschtein, Daniel

2011-01-01

The synergism between low-frequency sonophoresis (LFS) and chemical penetration enhancers (CPEs), especially surfactants, in transdermal enhancement has been investigated extensively since this phenomenon was first observed over a decade ago. In spite of the identifying that the origin of this synergism is the increased penetration and subsequent dispersion of CPEs in the skin in response to LFS treatment, to date, no mechanism has been directly proposed to explain how LFS induces the observed increased transport of CPEs. In this study, we propose a plausible physical mechanism by which the transport of all CPEs is expected to have significantly increased flux into the localized-transport regions (LTRs) of LFS-treated skin. Specifically, the collapse of acoustic cavitation microjets within LTRs induces a convective flux. In addition, because amphiphilic molecules preferentially adsorb onto the gas/water interface of cavitation bubbles, amphiphiles have an additional adsorptive flux. In this sense, the cavitation bubbles effectively act as carriers for amphiphilic molecules, delivering surfactants directly into the skin when they collapse at the skin surface as cavitation microjets. The flux equations derived for CPE delivery into the LTRs and non-LTRs during LFS treatment, compared to that for untreated skin, explain why the transport of all CPEs, and to an even greater extent amphiphilic CPEs, is increased during LFS treatment. The flux model is tested with a non-amphiphilic CPE (propylene glycol) and both nonionic and ionic amphiphilic CPEs (octyl glucoside and sodium lauryl sulfate, respectively), by measuring the flux of each CPE into untreated skin and the LTRs and non-LTRs of LFS-treated skin. The resulting data shows very good agreement with the proposed flux model. PMID:22100440

The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

PubMed

Zhu, Xianbing; Zeng, Xiaowei; Zhang, Xudong; Cao, Wei; Wang, Yilin; Chen, Houjie; Wang, Teng; Tsai, Hsiang-I; Zhang, Ran; Chang, Danfeng; He, Shuai; Mei, Lin; Shi, Xiaojun

2016-04-01

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect. Copyright © 2015 Elsevier Inc. All rights reserved.

An ultra-high performance liquid chromatography method to determine the skin penetration of an octyl methoxycinnamate-loaded liquid crystalline system.

PubMed

Prado, A H; Borges, M C; Eloy, J O; Peccinini, R G; Chorilli, M

2017-10-01

Cutaneous penetration is a critical factor in the use of sunscreen, as the compounds should not reach systemic circulation in order to avoid the induction of toxicity. The evaluation of the skin penetration and permeation of the UVB filter octyl methoxycinnamate (OMC) is essential for the development of a successful sunscreen formulation. Liquid-crystalline systems are innovative and potential carriers of OMC, which possess several advantages, including controlled release and protection of the filter from degradation. In this study, a new and effective method was developed using ultra-high performance liquid chromatography (UPLC) with ultraviolet detection (UV) for the quantitative analysis of penetration of OMC-loaded liquid crystalline systems into the skin. The following parameters were assessed in the method: selectivity, linearity, precision, accuracy, robustness, limit of detection (LOD), and limit of quantification (LOQ). The analytical curve was linear in the range from 0.25 to 250 μg.m-1, precise, with a standard deviation of 0.05-1.24%, with an accuracy in the range from 96.72 to 105.52%, and robust, with adequate values for the LOD and LOQ of 0.1 and 0.25 μg.mL -1, respectively. The method was successfully used to determine the in vitro skin permeation of OMC-loaded liquid crystalline systems. The results of the in vitro tests on Franz cells showed low cutaneous permeation and high retention of the OMC, particularly in the stratum corneum, owing to its high lipophilicity, which is desirable for a sunscreen formulation.

Monte Carlo study of skin optical clearing to enhance light penetration in the tissue: implications for photodynamic therapy of acne vulgaris

NASA Astrophysics Data System (ADS)

Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.; Altshuler, Gregory B.; Yaroslavsky, Ilya V.

2008-06-01

Result of Monte Carlo simulations of skin optical clearing is presented. The model calculations were carried out with the aim of studying of spectral response of skin under immersion liquids action and calculation of enhancement of light penetration depth. In summary, we have shown that: 1) application of glucose, propylene glycol and glycerol produced significant decrease of light scattering in different skin layers; 2) maximal clearing effect will be obtained in case of optical clearing of skin dermis, however, absorbed light fraction in skin dermis changed insignificantly, independently on clearing agent and place it administration; 3) in contrast to it, the light absorbed fraction in skin adipose layer increased significantly in case of optical clearing of skin dermis. It is very important because it can be used for development of optical methods of obesity treatment; 4) optical clearing of superficial skin layers can be used for decreasing of power of light radiation used for treatment of acne vulgaris.

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery.

PubMed

Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

2016-12-26

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w / w ), and a sodium deoxycholate gel (CP 0.05% w / w ) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery

PubMed Central

Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

2016-01-01

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w/w), and a sodium deoxycholate gel (CP 0.05% w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP. PMID:28035957

Enhanced skin permeation of naltrexone by pulsed electromagnetic fields in human skin in vitro.

PubMed

Krishnan, Gayathri; Edwards, Jeffrey; Chen, Yan; Benson, Heather A E

2010-06-01

The aim of the present study was to evaluate the skin permeation of naltrexone (NTX) under the influence of a pulsed electromagnetic field (PEMF). The permeation of NTX across human epidermis and a silicone membrane in vitro was monitored during and after application of the PEMF and compared to passive application. Enhancement ratios of NTX human epidermis permeation by PEMF over passive diffusion, calculated based on the AUC of cumulative NTX permeation to the receptor compartment verses time for 0-4 h, 4-8 h, and over the entire experiment (0-8 h) were 6.52, 5.25, and 5.66, respectively. Observation of the curve indicated an initial enhancement of NTX permeation compared to passive delivery whilst the PEMF was active (0-4 h). This was followed by a secondary phase after termination of PEMF energy (4-8 h) in which there was a steady increase in NTX permeation. No significant enhancement of NTX penetration across silicone membrane occurred with PEMF application in comparison to passively applied NTX. In a preliminary experiment PEMF enhanced the penetration of 10 nm gold nanoparticles through the stratum corneum as visualized by multiphoton microscopy. This suggests that the channels through which the nanoparticles move must be larger than the 10 nm diameter of these rigid particles. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

[Effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong and penetration mechanism of skin blood flow].

PubMed

Zhu, Xiao-Fang; Luo, Jing; Guan, Yong-Mei; Yu, Ya-Ting; Jin, Chen; Zhu, Wei-Feng; Liu, Hong-Ning

2017-02-01

The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong, and to investigate the possible penetration mechanism of their essential oil from the perspective of skin blood perfusion changes. Transdermal tests were performed in vitro with excised mice skin by improved Franz diffusion cells. The cumulative penetration amounts of ferulic acid in Chuanxiong were determined by HPLC to investigate the effects of Frankincense and Myrrh essential oil on transdermal permeation properties of Chuanxiong. Simultaneously, the skin blood flows were determined by laser flow doppler. The results showed that the cumulative penetration amount of ferulic acid in Chuanxiong was (8.13±0.76) μg•cm⁻² in 24 h, and was (48.91±4.87), (57.80±2.86), (63.34±4.56), (54.17±4.40), (62.52±7.79) μg•cm⁻² respectively in Azone group, Frankincense essential oil group, Myrrh essential oil, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group. The enhancement ratios of each essential oil groups were 7.68, 8.26, 7.26, 8.28, which were slightly greater than 6.55 in Azone group. In addition, as compared with the conditions before treatment, there were significant differences and obvious increasing trend in blood flow of rats in Frankincense essential oil group, Myrrh essential oil group, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group when were dosed at 10, 20, 30, 10 min respectively, indicating that the skin blood flows were increased under the effects of Frankincense and Myrrh essential oil to a certain extent. Thus, Frankincense and Myrrh essential oil had certain effect on promoting permeability of Chuanxiong both before and after drug combination, and may promote the elimination of drugs from epidermis to dermal capillaries through increase of

In vitro percutaneous penetration and characterization of silver from silver-containing textiles

PubMed Central

Bianco, Carlotta; Kezic, Sanja; Crosera, Matteo; Svetličić, Vesna; Šegota, Suzana; Maina, Giovanni; Romano, Canzio; Larese, Francesca; Adami, Gianpiero

2015-01-01

The objective of this study was to determine the in vitro percutaneous penetration of silver and characterize the silver species released from textiles in different layers of full thickness human skin. For this purpose, two different wound dressings and a garment soaked in artificial sweat were placed in the donor compartments of Franz cells for 24 hours. The concentration of silver in the donor phase and in the skin was determined by an electrothermal atomic absorption spectrometer (ET-AAS) and by inductively coupled plasma mass spectrometer (ICP-MS). The characterization of silver species in the textiles and in the skin layers was made by scanning electron microscopy with integrated energy dispersive X-ray spectroscopy (SEM-EDX). Additionally, the size distribution of silver nanoparticles in the textiles was performed by atomic force microscopy (AFM). On the surface of all investigated materials, silver nanoparticles of different size and morphology were found. Released silver concentrations in the soaking solutions (ie, exposure concentration) ranged from 0.7 to 4.7 μg/mL (0.6–4.0 μg/cm2), fitting the bactericidal range. Silver and silver chloride aggregates at sizes of up to 1 μm were identified both in the epidermis and dermis. The large size of these particles suggests that the aggregation occurred in the skin. The formation of these aggregates likely slowed down the systemic absorption of silver. Conversely, these aggregates may form a reservoir enabling prolonged release of silver ions, which might lead to local effects. PMID:25792824

Evaluation of filter media for particle number, surface area and mass penetrations.

PubMed

Li, Lin; Zuo, Zhili; Japuntich, Daniel A; Pui, David Y H

2012-07-01

The National Institute for Occupational Safety and Health (NIOSH) developed a standard for respirator certification under 42 CFR Part 84, using a TSI 8130 automated filter tester with photometers. A recent study showed that photometric detection methods may not be sensitive for measuring engineered nanoparticles. Present NIOSH standards for penetration measurement are mass-based; however, the threshold limit value/permissible exposure limit for an engineered nanoparticle worker exposure is not yet clear. There is lack of standardized filter test development for engineered nanoparticles, and development of a simple nanoparticle filter test is indicated. To better understand the filter performance against engineered nanoparticles and correlations among different tests, initial penetration levels of one fiberglass and two electret filter media were measured using a series of polydisperse and monodisperse aerosol test methods at two different laboratories (University of Minnesota Particle Technology Laboratory and 3M Company). Monodisperse aerosol penetrations were measured by a TSI 8160 using NaCl particles from 20 to 300 nm. Particle penetration curves and overall penetrations were measured by scanning mobility particle sizer (SMPS), condensation particle counter (CPC), nanoparticle surface area monitor (NSAM), and TSI 8130 at two face velocities and three layer thicknesses. Results showed that reproducible, comparable filtration data were achieved between two laboratories, with proper control of test conditions and calibration procedures. For particle penetration curves, the experimental results of monodisperse testing agreed well with polydisperse SMPS measurements. The most penetrating particle sizes (MPPSs) of electret and fiberglass filter media were ~50 and 160 nm, respectively. For overall penetrations, the CPC and NSAM results of polydisperse aerosols were close to the penetration at the corresponding median particle sizes. For each filter type, power

Impact of synthetic canine cerumen on in vitro penetration of auricular skin of dogs by florfenicol, terbinafine, and betamethasone acetate.

PubMed

Ehling, Sarah; Baynes, Ronald E; Bäumer, Wolfgang

2018-03-01

OBJECTIVE To determine the pharmacokinetics of florfenicol, terbinafine, and betamethasone acetate after topical application to canine auricular skin and the influence of synthetic canine cerumen on pharmacokinetics. SAMPLE Auricular skin from 6 euthanized shelter dogs (3 females and 3 neutered males with no visible signs of otitis externa). PROCEDURES Skin adjacent to the external opening of the ear canal was collected and prepared for use in a 2-compartment flow-through diffusion cell system to evaluate penetration of an otic gel containing florfenicol, terbinafine, and betamethasone acetate over a 24-hour period. Radiolabeled 14 C-terbinafine hydrochloride and 3 H-betamethasone acetate were added to the gel to determine dermal penetration and distribution. Florfenicol absorption was determined by use of high-performance liquid chromatography-UV detection. Additionally, the effect of synthetic canine cerumen on the pharmacokinetics of all compounds was evaluated. RESULTS During the 24-hour experiment, mean ± SD percentage absorption without the presence of synthetic canine cerumen was 0.28 ± 0.09% for 3H-betamethasone acetate, 0.06 ± 0.06% for florfenicol, and 0.06 ± 0.02% for 14C-terbinafine hydrochloride. Absorption profiles revealed no impact of synthetic canine cerumen on skin absorption for all 3 active compounds in the gel or on skin distribution of 3 H-betamethasone acetate and 14 C-terbinafine hydrochloride. CONCLUSIONS AND CLINICAL RELEVANCE 3 H-betamethasone acetate, 14 C-terbinafine hydrochloride, and florfenicol were all absorbed in vitro through healthy auricular skin specimens within the first 24 hours after topical application. Synthetic canine cerumen had no impact on dermal absorption in vitro, but it may serve as a temporary reservoir that prolongs the release of topical drugs.

Fractional laser microablation of skin: increasing the efficiency of transcutaneous delivery of particles

NASA Astrophysics Data System (ADS)

Genina, E. A.; Dolotov, L. E.; Bashkatov, A. N.; Tuchin, V. V.

2016-06-01

We study several regimes of fractional laser microablation using a pulsed Er : YAG laser for producing microchannels of different depth and incisions that allow transcutaneous delivery of particles of different size, namely, Al2O3 (27 μm), ZrO2 (smaller than 5 μm) and TiO2 (smaller than 100 nm). The shock wave regime was used both for enhancing the penetration of particles into the ablation zones and as an independent method of particle delivery into the skin. Based on optical coherence tomography we assessed the coherent depth of particle detection in the skin in 2 hours, 3 days and 10 days after the administration. The maximal localisation depth (up to 450 μm) was obtained for TiO2 nanoparticles in the regime of incisions with enhancement of particle penetration by pulses of a multiple-beam hydrodynamic shock wave. The results of the study can be useful for developing new methods of transcutaneous delivery of micro- and nanocarriers of medicinal preparations.

Engineered inorganic nanoparticles and cosmetics: facts, issues, knowledge gaps and challenges.

PubMed

Wiechers, Johann W; Musee, Ndeke

2010-10-01

The cosmetic industry is among the first adaptors of nanotechnology through the use of engineered nanoparticles (ENPs) to enhance the performance of their products and meet the customers' needs. Recently, there have been increasing concerns from different societal stakeholders (e.g., governments, environmental activist pressure groups, scientists, general public, etc.) concerning the safety and environmental impact of ENPs used in cosmetics. This review paper seeks to address the twin concerns of the safety of cosmetics and the potential environmental impacts due to the constituent chemicals-the ENPs. The safety aspect is addressed by examining recently published scientific data on the possibility of ENPs penetrating human skin. Data indicates that although particular types of ENPs can penetrate into the skin, until now no penetration has been detected beyond the stratum corneum of the ENPs used in cosmetics. Yet, important lessons can be learned from the more recent studies that identify the characteristics of ENPs penetrating into and permeating through human skin. On the part of the environmental impact, the scientific literature has very limited or none existent specific articles addressing the environmental impacts of ENPs owing to the cosmetic products. Therefore, general ecotoxicological data on risk assessment of ENPs has been applied to ascertain if there are potential environmental impacts from cosmetics. Results include some of the first studies on the qualitative and quantitative risk assessment of ENPs from cosmetics and suggest that further research is required as the knowledge is incomplete to make definitive conclusions as is the case with skin penetration. The authors conclude that the cosmetic industry should be more transparent in its use of nanotechnology in cosmetic products to facilitate realistic risk assessments as well as scientists and pressure groups being accurate in their conclusions on the general applicability of their findings

Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress

PubMed Central

Lin, Zih-Chan; Lee, Chiang-Wen; Tsai, Ming-Horng; Ko, Horng-Huey; Fang, Jia-You; Chiang, Yao-Chang; Liang, Chan-Jung; Hsu, Lee-Fen; Hu, Stephen Chu-Sung; Yen, Feng-Lin

2016-01-01

Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora, has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation. PMID:27570454

Effects of soap-water wash on human epidermal penetration.

PubMed

Zhu, Hanjiang; Jung, Eui-Chang; Phuong, Christina; Hui, Xiaoying; Maibach, Howard

2016-08-01

Skin decontamination is a primary interventional method used to decrease dermal absorption of hazardous contaminants, including chemical warfare agents, pesticides and industrial pollutants. Soap and water wash, the most common and readily available decontamination system, may enhance percutaneous absorption through the "wash-in effect." To understand better the effect of soap-water wash on percutaneous penetration, and provide insight to improving skin decontamination methods, in vitro human epidermal penetration rates of four C(14) -labeled model chemicals (hydroquinone, clonidine, benzoic acid and paraoxon) were assayed using flow-through diffusion cells. Stratum corneum (SC) absorption rates of these chemicals at various hydration levels (0-295% of the dry SC weights) were determined and compared with the results of the epidermal penetration study to clarify the effect of SC hydration on skin permeability. Results showed accelerated penetration curves of benzoic acid and paraoxon after surface wash at 30 min postdosing. Thirty minutes after washing (60 min postdosing), penetration rates of hydroquinone and benzoic acid decreased due to reduced amounts of chemical on the skin surface and in the SC. At the end of the experiment (90 min postdosing), a soap-water wash resulted in lower hydroquinone penetration, greater paraoxon penetration and similar levels of benzoic acid and clonidine penetration compared to penetration levels in the non-wash groups. The observed wash-in effect agrees with the enhancement effect of SC hydration on the SC chemical absorption rate. These results suggest SC hydration derived from surface wash to be one cause of the wash-in effect. Further, the occurrence of a wash-in effect is dependent on chemical identity and elapsed time between exposure and onset of decontamination. By reducing chemical residue quantity on skin surface and in the SC reservoir, the soap-water wash may decrease the total quantity of chemical absorbed in the

Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals.

PubMed

Puglia, Carmelo; Bonina, Francesco

2012-04-01

Lipid nanoparticles are innovative carrier systems developed as an alternative to traditional vehicles such as emulsions, liposomes and polymeric nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured lipid carriers (NLC) show important advantages for dermal application of cosmetics and pharmaceuticals. This article focuses on the main features of lipid nanoparticles, in terms of their preparation and recent advancements. A detailed review of the literature is presented, introducing the importance of these systems in the topical delivery of drugs and active substances. Lipid nanoparticles are able to enhance drug penetration into the skin, allowing increased targeting to the epidermis and consequently increasing treatment efficiency and reducing the systemic absorption of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles and their biocompatible chemical nature have secured them the title of 'nanosafe carriers.' SLN and NLC represent a new technological era, which has been taken over by the cosmetic and pharmaceutical industry, which will open new channels for effective topical delivery of substances.

Enhanced stability and dermal delivery of hydroquinone using solid lipid nanoparticles.

PubMed

Ghanbarzadeh, Saeed; Hariri, Reza; Kouhsoltani, Maryam; Shokri, Javad; Javadzadeh, Yousef; Hamishehkar, Hamed

2015-12-01

Hydroquinone (HQ), a well-known anti-hyperpigmentation agent suffers from (a) instability due to rapid oxidation, (b) insufficient skin penetration because of hydrophilic structure, and (c) severe side effects as a results of systemic absorption. This study aimed to load HQ into solid lipid nanoparticles (SLNs) to overcome the mentioned drawbacks for the efficient treatment of hyperpigmentation. The optimized SLN formulation was prepared by hot melt homogenization method and fully characterized by various techniques. The ability of SLNs in dermal delivery of HQ was assessed through the excised rat skin. The optimized HQ-loaded SLNs (particle size of 86 nm, encapsulation efficiency% of 89.5% and loading capacity% of 11.2%) exhibited a good physicochemical stability during a period of five months. XRD and DSC results showed that HQ was dispersed in an amorphous state, confirming uniform drug dispersion in the SLNs structure and embedment of drug in the solid lipid matrix. In vitro penetration studies showed almost 3 times higher drug accumulation in the skin and 6.5 times lower drug entrance to receiving compartment of Franz diffusion cell from HQ-loaded SLN hydrogel compared with HQ Carbopol made hydrogel. These results indicated the better HQ localization in the skin and its lower systemic absorption. It was concluded that SLN is a promising colloidal drug carrier for topical administration of HQ in the treatment of hyperpigmentation due to suitable HQ loading value in spite of its hydrophilic structure, high stability against oxidation and appropriate skin penetration along with the low systemic absorption. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo.

PubMed

Freimann, Krista; Arukuusk, Piret; Kurrikoff, Kaido; Pärnaste, Ly; Raid, Raivo; Piirsoo, Andres; Pooga, Margus; Langel, Ülo

2018-03-02

Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential. Using previously designed efficient cell-penetrating peptide NF55, we searched for strategies enabling control over the nanoparticle formation and properties to further improve transfection efficacy. The size of the NF55/pDNA nanoparticles correlates with the concentration of its constituents at the beginning of assembly, but characteristics of nanoparticles measured by DLS do not reliably predict the applicability of particles in in vivo studies. We introduce a new formulation approach called cryo-concentration, where we acquired stable and homogeneous nanoparticles for administration in vivo. The cryo-concentrated NF55/pDNA nanoparticles exhibit several advantages over standard formulation: They have long shelf-life and do not aggregate after reconstitution, have excellent stability against enzymatic degradation, and show significantly higher bioactivity in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Titanium Nanoparticle Size Influences Trace Concentration Levels in Skin Appendages.

PubMed

Tasat, Deborah R; Domingo, Mariela G; Bruno, Marcos E; Guglielmotti, María B; Olmedo, Daniel G

2017-07-01

As a result of biotribocorrosion, the surface of a titanium (Ti) biomedical device can be a potential source of systemic contamination with Ti nanoparticles (NPs). Although NPs can be chemically similar, differences in particle size may lead to different biological responses. The aim of this experimental study was to determine Ti trace levels in skin appendages and plasma and explore the influence of NP size on trace levels using a murine model. Results showed the presence of Ti traces in the nails, hair, and plasma. The concentration of the smallest NPs (5 Nm) was higher than that of 10 Nm NPs in all the studied samples. Irrespective of NP size, Ti levels were always lower in plasma than in skin appendages. Ti levels were higher in nails than in hair. Ti NPs size influenced trace concentration levels in hair/nails, suggesting that 5 Nm Ti particles are more easily eliminated through these skin appendages. Given that the nails showed the highest levels of Ti, and that these skin appendages are not exposed to agents that can leach out Ti, as occurs with hair, we propose the nails as the most suitable and reliable bioindicator for monitoring systemic contamination with Ti.

Nanoparticles Penetrate into the Multicellular Spheroid-on-Chip: Effect of Surface Charge, Protein Corona, and Exterior Flow.

PubMed

Huang, Ke; Boerhan, Rena; Liu, Changming; Jiang, Guoqiang

2017-12-04

Nanoparticles (NPs) are widely studied as tumor targeted vehicles. The penetration of NPs into the tumor is considered as a major barrier for delivery of NPs into tumor cell and a big challenge to translate NPs from lab to the clinic. The objective of this study is to know how the surface charge of NPs, the protein corona surrounding the NPs, and the fluid flow around the tumor surface affect the penetration and accumulation of NPs into the tumor, through in vitro penetration study based on a spheroid-on-chip system. Surface decorated polystyrene (PS) NPs (100 nm) carrying positive and negative surface charge were loaded to the multicellular spheroids under static and flow conditions, in the presence or absence of serum proteins. NP penetration was investigated by confocal laser microscopy scanning followed with quantitative image analysis. The results reveal that negatively charged NPs are attached more on the spheroid surface and easier to penetrate into the spheroids. Protein corona, which is formed surrounding the NPs in the presence of serum protein, changes the surface properties of the NPs, weakens the NP-cell affinity, and, therefore, results in lower NP concentration on the spheroid surface but might facilitate deeper penetration. The exterior fluid flow enhances the interstitial flow into the spheroid, which benefits the penetration but also strips the NPs (especially the NPs with protein corona) on the spheroid surface, which decreases the penetration flux significantly. The maximal penetration was obtained by applying negatively charged NPs without protein corona under the flow condition. We hope the present study will help to understand the spatiotemporal performance of drug delivery NPs and inform the rational design of NPs with highly defined drug accumulation localized at a target site.

Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil.

PubMed

Mura, Simona; Manconi, Maria; Sinico, Chiara; Valenti, Donatella; Fadda, Anna Maria

2009-10-01

The aim of this work was to evaluate the ability of a few different penetration enhancers to produce elastic vesicles with soy lecithin and the influence of the obtained vesicles on in vitro (trans)dermal delivery of minoxidil. To this purpose, so-called Penetration Enhancer-containing Vesicles (PEVs) were prepared as dehydrated-rehydrated vesicles by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy)ethanol (Transcutol), capryl-caproyl macrogol 8-glyceride (Labrasol), and cineole. Soy lecithin liposomes, without penetration enhancers, were used as control. Prepared formulations were characterized in terms of size distribution, morphology, zeta potential, and vesicle deformability. The influence of PEVs on (trans)dermal delivery of minoxidil was studied by in vitro diffusion experiments through newborn pig skin in comparison with traditional liposomes and ethanolic solutions of the drug also containing each penetration enhancer. A skin pre-treatment study using empty PEVs and conventional liposomes was also carried out. Results showed that all the used penetration enhancers were able to give more deformable vesicles than conventional liposomes with a good drug entrapment efficiency and stability. In vitro skin penetration data showed that PEVs were able to give a statistically significant improvement of minoxidil deposition in the skin in comparison with classic liposomes and penetration enhancer-containing drug ethanolic solutions without any transdermal delivery. Moreover, the most deformable PEVs, prepared with Labrasol and cineole, were also able to deliver to the skin a higher total amount of minoxidil than the PE alcoholic solutions thus suggesting that minoxidil delivery to the skin was strictly correlated to vesicle deformability, and therefore to vesicle composition.

Hydrocortisone Diffusion Through Synthetic Membrane, Mouse Skin, and Epiderm™ Cultured Skin

PubMed Central

Christensen, John Mark; Chuong, Monica Chang; Le, Hang; Pham, Loan; Bendas, Ehab

2011-01-01

Objectives The penetration of hydrocortisone (HC) from six topical over-the-counter products along with one prescription cream through cultured normal human-derived epidermal keratinocytes (Epiderm™), mouse skin and synthetic nylon membrane was performed as well as the effect hydrating the skin by pre-washing was explored using the Upright Franz Cell. Method and Results Permeation of HC through EpiDerm™, mouse skin and synthetic membrane was highest with the topical HC gel formulation with prewash treatment of the membranes among seven products evaluated, 198 ± 32 µg/cm2, 746.32 ± 12.43 µg/cm2, and 1882 ± 395.18 µg/cm2, respectively. Pre-washing to hydrate the skin enhanced HC penetration through EpiDerm™ and mouse skin. The 24-hour HC released from topical gel with prewash treatment was 198.495 ± 32 µg/cm2 and 746.32 ± 12.43 µg/cm2 while without prewash, the 24-h HC released from topical gel was 67.2 ± 7.41 µg/cm2 and 653.43 ± 85.62 µg/cm2 though EpiDerm™ and mouse skin, respectively. HC penetration through synthetic membrane was ten times greater than through mouse skin and EpiDerm™. Generally, the shape, pattern, and rank order of HC diffusion from each commercial product was similar through each membrane. PMID:21572515

The design of naproxen solid lipid nanoparticles to target skin layers.

PubMed

Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Rostamkalaei, Seyyed Sohrab; Asadi, Masoumeh; Asare-Addo, Kofi; Nokhodchi, Ali

2016-09-01

The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257±4.852nm to 143.90±2.685nm and from 0.293±0.037 to 0.525±0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE%). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the

Complex formation of sericoside with hydrophilic cyclodextrins: improvement of solubility and skin penetration in topical emulsion based formulations.

PubMed

Rode, T; Frauen, M; Müller, B W; Düsing, H J; Schönrock, U; Mundt, C; Wenck, H

2003-03-01

The main objective of this study was to devise novel methods for improving the solubility of the anti-inflammatory triterpenoid sericoside, the main component of Terminalia sericea extract, thus enabling its incorporation into topical formulations. Sericoside was stabilized by complex formation with hydrophilic derivatives of beta- and gamma-cyclodextrins in a molar ratio of 1.0:1.1. The complex of extract and cyclodextrin was equilibrated in water at 25 degrees C for approximately 24 h. The dehydrated complexes of T. sericea extract and cyclodextrin were characterized by differential scanning calorimetry, thermogravimetry analysis and X-ray diffraction. Complex formation with beta-cyclodextrin as well as gamma-cyclodextrin derivatives was detectable using these three analytical tools; however, only complexes with gamma-cyclodextrin derivatives showed stability upon storage after incorporation into topical o/w or w/o formulations. Furthermore, a T. sericea extract/gamma-cyclodextrin complex incorporated in an o/w formulation resulted in a 2.6-fold higher percutaneous penetration of sericoside in in vitro excised pig skin as compared to pure T. sericea extract. For the first time, the virtually insoluble anti-inflammatory active sericoside was incorporated into a topical emulsion based formulation in a stable manner, resulting in efficient skin penetration. Copyright 2003 Elsevier Science B.V.

Simple amides of oleanolic acid as effective penetration enhancers.

PubMed

Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

2015-01-01

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

Simple Amides of Oleanolic Acid as Effective Penetration Enhancers

PubMed Central

Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

2015-01-01

Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented. PMID:26010090

Magnetoconductance oscillations at a nanoparticle film-superconductor interface: a means for probing flux penetration depth.

PubMed

Dunford, Jeffrey L; Dhirani, Al-Amin

2008-11-12

Interfaces between disordered normal materials and superconductors (S) can exhibit 'reflectionless tunnelling' (RT)-a phenomenon that arises from repeated disorder-driven elastic scattering, multiple Andreev reflections, and electron/hole interference. RT has been used to explain zero-bias conductance peaks (ZBCPs) observed using doped semiconductors and evaporated granular metal films as the disordered normal materials. Recently, in addition to ZBCPs, magnetoconductance oscillations predicted by RT theory have been observed using a novel normal disordered material: self-assembled nanoparticle films. In the present study, we find that the period of these oscillations decreases as temperature (T) increases. This suggests that the magnetic flux associated with interfering pathways increases accordingly. We propose that the increasing flux can be attributed to magnetic field penetration into S as [Formula: see text]. This model agrees remarkably well with known T dependence of penetration depth predicted by Bardeen-Cooper-Schrieffer theory. Our study shows that this additional region of flux is significant and must be considered in experimental and theoretical studies of RT.

High resolution SEM imaging of gold nanoparticles in cells and tissues.

PubMed

Goldstein, A; Soroka, Y; Frušić-Zlotkin, M; Popov, I; Kohen, R

2014-12-01

The growing demand of gold nanoparticles in medical applications increases the need for simple and efficient characterization methods of the interaction between the nanoparticles and biological systems. Due to its nanometre resolution, modern scanning electron microscopy (SEM) offers straightforward visualization of metallic nanoparticles down to a few nanometre size, almost without any special preparation step. However, visualization of biological materials in SEM requires complicated preparation procedure, which is typically finished by metal coating needed to decrease charging artefacts and quick radiation damage of biomaterials in the course of SEM imaging. The finest conductive metal coating available is usually composed of a few nanometre size clusters, which are almost identical to the metal nanoparticles employed in medical applications. Therefore, SEM monitoring of metal nanoparticles within cells and tissues is incompatible with the conventional preparation methods. In this work, we show that charging artefacts related to non-conductive biological specimen can be successfully eliminated by placing the uncoated biological sample on a conductive substrate. By growing the cells on glass pre-coated with a chromium layer, we were able to observe the uptake of 10 nm gold nanoparticles inside uncoated and unstained macrophages and keratinocytes cells. Imaging in back scattered electrons allowed observation of gold nanoparticles located inside the cells, while imaging in secondary electron gave information on gold nanoparticles located on the surface of the cells. By mounting a skin cross-section on an improved conductive holder, consisting of a silicon substrate coated with copper, we were able to observe penetration of gold nanoparticles of only 5 nm size through the skin barrier in an uncoated skin tissue. The described method offers a convenient modification in preparation procedure for biological samples to be analyzed in SEM. The method provides high

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery.

PubMed

Kanikkannan, N; Kandimalla, K; Lamba, S S; Singh, M

2000-06-01

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain

Quantification of skin penetration of antioxidants of varying lipophilicity.

PubMed

Abla, M J; Banga, A K

2013-02-01

Antioxidants play a vital role in protecting the skin from environmental distress. As the skin is constantly exposed to harmful UV radiation, endogenous antioxidants present in the superficial layers of the skin neutralize reactive oxygen species. Over time, antioxidants become depleted and loss their protective effect on the skin. Therefore, supplementing skin with topical antioxidant can help replenish this loss and fight the oxidative stress. The objective of this study was to deliver antioxidants topically and quantify the amount permeated in the stratum corneum and underlying skin. Polyphenols (catechin, resveratrol and curcumin) and vitamin (retinol) with various lipophilic properties were delivered via porcine ear skin, using propylene glycol as a vehicle. The amount in the stratum corneum and underlying skin was quantified using tape stripping and skin extraction methods, respectively, and samples were analysed via HPLC. All four antioxidants permeated into the skin from the propylene glycol vehicle. The order of the amount of antioxidant in the stratum corneum was catechin > resveratrol~ retinol> curcumin, whereas that in the underlying skin was retinol > catechin~ resveratrol~ curcumin. Of the total amount of polyphenols in the skin, approximately 90% was retained in the stratum corneum whereas 10% was quantified in the underlying skin. In contrast, 10% of retinol was retained in the stratum corneum whereas 90% permeated in the underlying skin. Polyphenols (catechin, resveratrol and curcumin) showed high concentration in the stratum corneum whereas retinol showed high accumulation in the underlying layers of the skin. © 2012 The Authors ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Ultrasound-facilitated transport of silver chloride (AgCl) particles in fish skin.

PubMed

Frenkel, V; Kimmel, E; Iger, Y

2000-08-10

Electron-dense nano-particles in aqueous suspension were administered by immersion into the epidermis of fish using ultrasound in the therapeutic range. Enhanced permeability of the tissues to the particles was achieved by acoustic cavitation, which induced a controlled level of necrosis in the outer cell layers, and by non-cavitational exposures, which widened intercellular spaces of non-necrosed tissue in deeper regions of the epidermis. Both particle concentration and penetration depth were quantified using transmission electron microscopy. While cavitation-induced perforation was necessary for particles to penetrate into the tissues, non-cavitational exposures during immersions increased the particle flux towards the skin surface, as well as the diffusion rate of the particles within the epidermis and their depth of penetration. The technique described above may potentially be applied for non-stressful, mass-administration of substances into aquatic animals, as well as the relatively new field of ultrasound-facilitated delivery in moist epithelial tissues in humans.

Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance.

PubMed

Todosijević, Marija N; Savić, Miroslav M; Batinić, Bojan B; Marković, Bojan D; Gašperlin, Mirjana; Ranđelović, Danijela V; Lukić, Milica Ž; Savić, Snežana D

2015-12-30

To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09μg/cm(2), and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor.

PubMed

Xie, Feng; Chai, Jia-Ke; Hu, Quan; Yu, Yong-Hui; Ma, Li; Liu, Ling-Ying; Zhang, Xu-Long; Li, Bai-Ling; Zhang, Dong-Hai

2016-06-30

The aim of the present study was to investigate the potential application of (+)-camphor as a penetration enhancer for the transdermal delivery of drugs with differing lipophilicity. The skin irritation of camphor was evaluated by in vitro cytotoxicity assays and in vivo transdermal water loss (TEWL) measurements. A series of model drugs with a wide span of lipophilicity (logP value ranging from 3.80 to -0.95), namely indometacin, lidocaine, aspirin, antipyrine, tegafur and 5-fluorouracil, were tested using in vitro transdermal permeation experiments to assess the penetration-enhancing profile of camphor. Meanwhile, the in vivo skin microdialysis was carried out to further investigate the enhancing effect of camphor on the lipophilic and hydrophilic model drugs (i.e. lidocaine and tegafur). SC (stratum corneum)/vehicle partition coefficient and Fourier transform infrared spectroscopy (FTIR) were performed to probe the regulation action of camphor in the skin permeability barrier. It was found that camphor produced a relatively low skin irritation, compared with the frequently-used and standard penetration enhancer laurocapram. In vitro skin permeation studies showed that camphor could significantly facilitate the transdermal absorption of model drugs with differing lipophilicity, and the penetration-enhancing activities were in a parabola curve going downwards with the drug logP values, which displayed the optimal penetration-enhancing efficiency for the weak lipophilic or hydrophilic drugs (an estimated logP value of 0). In vivo skin microdialysis showed that camphor had a similar penetration behavior on transdermal absorption of model drugs. Meanwhile, the partition of lipophilic drugs into SC was increased after treatment with camphor, and camphor also produced a shift of CH2 vibration of SC lipid to higher wavenumbers and decreased the peak area of the CH2 vibration, probably resulting in the alteration of the skin permeability barrier. This suggests that

Skin penetration assessment of less lethal kinetic energy munitions.

PubMed

Bir, Cynthia A; Stewart, Shelby J; Wilhelm, Marianne

2005-11-01

The development of less-lethal technologies has provided law enforcement personnel with an alternative to lethal force. Although the less lethal projectile was produced to engender non-penetrating wounds, case studies show that there have been a number of reported penetrating injuries ranging from minor to significant in morbidity. The objective of this study was to determine the energy per unit area required to penetrate various regions of the body. Eight unembalmed postmortem human specimens were procured for this testing. Each specimen sustained a maximum of 25 impacts consisting of shots to the anterior and posterior thorax, abdomen, and legs. A 12-gauge, fin-stabilized, rubber rocket round was used as the impactor for all of the conducted tests. The energy density required for 50% risk of penetration varied from 23.99 J/cm2 for the location on the anterior rib (p = 0.000) to 52.74 J/cm2 for the location on the posterior rib (p = 0.001).

A comparative study on the transdermal penetration effect of gaseous and aqueous plasma reactive species

NASA Astrophysics Data System (ADS)

Liu, Xin; Gan, Lu; Ma, Mingyu; Zhang, Song; Liu, Jingjing; Chen, Hongxiang; Liu, Dawei; Lu, Xinpei

2018-02-01

To improve the depth of plasma active species in the skin, it is very important to develop skin disease treatment using plasma. In this article, an air plasma source was used to work directly with the skin of a mouse. A tortuous pathway, hair follicles, electroporation and a microneedle do not aid the transdermal delivery of gaseous plasma active species, therefore these gaseous plasma active species cannot penetrate mouse skin with a thickness of ~0.75 mm. The plasma activated water (PAW) produced by the air plasma source was used to study the transdermal penetration of the aqueous plasma activated species. This aqueous plasma activated species can penetrate the skin through hair follicles, intercellular and transcellular routes. The pH of the PAW did not affect the penetration efficiency of the aqueous plasma active species.

Electrochemical monitoring of native catalase activity in skin using skin covered oxygen electrode.

PubMed

Nocchi, Sarah; Björklund, Sebastian; Svensson, Birgitta; Engblom, Johan; Ruzgas, Tautgirdas

2017-07-15

A skin covered oxygen electrode, SCOE, was constructed with the aim to study the enzyme catalase, which is part of the biological antioxidative system present in skin. The electrode was exposed to different concentrations of H 2 O 2 and the amperometric current response was recorded. The observed current is due to H 2 O 2 penetration through the outermost skin barrier (referred to as the stratum corneum, SC) and subsequent catalytic generation of O 2 by catalase present in the underlying viable epidermis and dermis. By tape-stripping the outermost skin layers we demonstrate that SC is a considerable diffusion barrier for H 2 O 2 penetration. Our experiments also indicate that skin contains a substantial amount of catalase, which is sufficient to detoxify H 2 O 2 that reaches the viable epidermis after exposure of skin to high concentrations of peroxide (0.5-1mM H 2 O 2 ). Further, we demonstrate that the catalase activity is reduced at acidic pH, as compared with the activity at pH 7.4. Finally, experiments with often used penetration enhancer thymol shows that this compound interferes with the catalase reaction. Health aspect of this is briefly discussed. Summarizing, the results of this work show that the SCOE can be utilized to study a broad spectrum of issues involving the function of skin catalase in particular, and the native biological antioxidative system in skin in general. Copyright © 2017 Elsevier B.V. All rights reserved.

Temperature-Enhanced Follicular Penetration of Thermoresponsive Nanogels

NASA Astrophysics Data System (ADS)

Jung, Sora; Nagel, Gregor; Giulbudagian, Michael; Calderón, Marcelo; Patzelt, Alexa; Knorr, Fanny; Lademann, Jürgen

2018-05-01

Hair follicles can serve as an effective reservoir for dermal drug delivery upon the topical application of particulate substances. Here, the follicular penetration of an indodicarbocyanine-labelled thermoresponsive nanogel (189 nm) having a cloud point temperature of 34°C and linked via an acid-labile linker to the model drug indocarbocyanine was investigated. In total, 227 hair follicles of porcine ear skin were examined after topical application of the thermoresponsive nanogels at room temperature (21°C), physiological skin surface temperature (32°C) and core body temperature (37°C) for the follicular penetration depths of indodicarbocyanine and indocarbocyanine using confocal laser scanning microscopy. The results showed a significantly increased mean follicular penetration of the carrier to a depth of 298.8±85.8 μm after incubation at 37°C compared to samples incubated at 21°C and 32°C with mean follicular penetration depths of 202.7±81.7 μm and 219.4±52.9 μm, respectively (p<0.001). Possibly structural changes in the thermoresponsive nanogel induced by the increased incubation temperature led to an enhancement of follicular penetration. Therefore, thermoresponsive nanogels may be suitable for the temperature-enhanced penetration into the hair follicles under physiological conditions.

Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin.

PubMed

Thors, L; Koch, M; Wigenstam, E; Koch, B; Hägglund, L; Bucht, A

2017-08-01

The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water). The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX. In conclusion, early initiated decontamination with the

Modelling the effect of mixture components on permeation through skin.

PubMed

Ghafourian, T; Samaras, E G; Brooks, J D; Riviere, J E

2010-10-15

A vehicle influences the concentration of penetrant within the membrane, affecting its diffusivity in the skin and rate of transport. Despite the huge amount of effort made for the understanding and modelling of the skin absorption of chemicals, a reliable estimation of the skin penetration potential from formulations remains a challenging objective. In this investigation, quantitative structure-activity relationship (QSAR) was employed to relate the skin permeation of compounds to the chemical properties of the mixture ingredients and the molecular structures of the penetrants. The skin permeability dataset consisted of permeability coefficients of 12 different penetrants each blended in 24 different solvent mixtures measured from finite-dose diffusion cell studies using porcine skin. Stepwise regression analysis resulted in a QSAR employing two penetrant descriptors and one solvent property. The penetrant descriptors were octanol/water partition coefficient, logP and the ninth order path molecular connectivity index, and the solvent property was the difference between boiling and melting points. The negative relationship between skin permeability coefficient and logP was attributed to the fact that most of the drugs in this particular dataset are extremely lipophilic in comparison with the compounds in the common skin permeability datasets used in QSAR. The findings show that compounds formulated in vehicles with small boiling and melting point gaps will be expected to have higher permeation through skin. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.396. The chemical space of the dataset was compared with that of the known skin permeability datasets and gaps were identified for future skin permeability measurements. Copyright 2010 Elsevier B.V. All rights reserved.

Active Silver Nanoparticles for Wound Healing

PubMed Central

Rigo, Chiara; Ferroni, Letizia; Tocco, Ilaria; Roman, Marco; Munivrana, Ivan; Gardin, Chiara; Cairns, Warren R. L.; Vindigni, Vincenzo; Azzena, Bruno; Barbante, Carlo; Zavan, Barbara

2013-01-01

In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial activity, while cellular staining techniques show that nuclear integrity is maintained, with no signs of cell death. For the first time, transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) analyses were carried out on skin biopsies taken from a single patient during treatment. The results show that Ag NPs are released as aggregates and are localized in the cytoplasm of fibroblasts. No signs of cell death were observed, and the nanoparticles had different distributions within the cells of the upper and lower dermis. Depth profiles of the Ag concentrations were determined along the skin biopsies. In the healed sample, most of the silver remained in the surface layers, whereas in the unhealed sample, the silver penetrated more deeply. The Ag concentrations in the cell cultures were also determined. Clinical observations and experimental data collected here are consistent with previously published articles and support the safety of Ag NP-based dressing in wound treatment. PMID:23455461

Amperometric monitoring of quercetin permeation through skin membranes.

PubMed

Rembiesa, Jadwiga; Gari, Hala; Engblom, Johan; Ruzgas, Tautgirdas

2015-12-30

Transdermal delivery of quercetin (QR, 3,3',4',5,7-pentahydroxyflavone), a natural flavonoid with a considerable antioxidant capacity, is important for medical treatment of, e.g., skin disorders. QR permeability through skin is low, which, at the same time, makes the monitoring of percutaneous QR penetration difficult. The objective of this study was to assess an electrochemical method for monitoring QR penetration through skin membranes. An electrode was covered with the membrane, exposed to QR solution, and electrode current was measured. The registered current was due to electro-oxidation of QR penetrating the membrane. Exploiting strict current-QR flux relationships diffusion coefficient, D, of QR in skin and dialysis membranes was calculated. The D values were strongly dependent on the theoretical model and parameters assumed in the processing of the amperometric data. The highest values of D were in the range of 1.6-6.1×10(-7)cm(2)/s. This was reached only for skin membranes pretreated with buffer-ethanol mixture for more than 24h. QR solutions containing penetration enhancers, ethanol and l-menthol, definitely increased D values. The results demonstrate that electrochemical setup gives a possibility to assess penetration characteristics as well as enables monitoring of penetration dynamics, which is more difficult by traditional methods using Franz cells. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro skin decontamination of the organophosphorus pesticide Paraoxon with nanometric cerium oxide CeO2.

PubMed

Salerno, Alicia; Devers, Thierry; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Josse, Denis; Briançon, Stéphanie

2017-04-01

Organophosphorus compounds (OP), which mainly penetrate via the percutaneous pathway, represent a threat for both military and civilians. Body surface decontamination is vital to prevent victims poisoning. The development of a cost-effective formulation, which could be efficient and easy to handle in case of mass contamination, is therefore crucial. Metal oxides nanoparticles, due their large surface areas and the large amount of highly reactive sites, present high reactivity towards OP. First, this study aimed at evaluating the reaction of CeO 2 nanoparticles, synthetized by microwave path and calcined at 500 or 600 °C, with Paraoxon (POX) in aqueous solution. Results showed that both nanoparticles degraded 60%-70% of POX. CeO 2 calcined at 500 °C, owing to its larger specific area, was the most effective. Moreover, the degradation was significantly increased under Ultra-Violet irradiation (initial degradation rate doubled). Then, skin decontamination was studied in vitro using the Franz cell method with pig-ear skin samples. CeO 2 powder and an aqueous suspension of CeO 2 (CeO 2 -W) were applied 1 h after POX exposure. The efficiency of decontamination, including removal and/or degradation of POX, was compared to Fuller's earth (FE) and RSDL lotion which are, currently, the most efficient systems for skin decontamination. CeO 2 -W and RSDL were the most efficient to remove POX from the skin surface and decrease skin absorption by 6.4 compared to the control not decontaminated. FE reduced significantly (twice) the absorbed fraction of POX, contrarily to CeO 2 powder. Considering only the degradation rate of POX, the products ranged in the order CeO 2  > RSDL > CeO 2 -W > FE (no degradation). This study showed that CeO 2 nanoparticles are a promising material for skin decontamination of OP if formulated as a dispersion able to remove POX like CeO 2 -W and to degrade it as CeO 2 powder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids.

PubMed

Kulkarni, Prajakta; Haldar, Manas K; Katti, Preeya; Dawes, Courtney; You, Seungyong; Choi, Yongki; Mallik, Sanku

2016-08-17

Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide-lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions.

A Double-Blind Study on Acupuncture Sensations with Japanese Style of Acupuncture: Comparison between Penetrating and Placebo Needles.

PubMed

Nishiwaki, Masako; Takayama, Miho; Yajima, Hiroyoshi; Nasu, Morihiro; Park, Joel; Kong, Jian; Takakura, Nobuari

2018-01-01

To investigate the acupuncture sensations elicited by the Japanese style of acupuncture, penetrating acupuncture and skin-touch placebo needles were randomly administered at various insertion depths (5 and 10 mm for the penetrating needles and 1 and 2 mm for the placebo needles) at LI4 to 50 healthy subjects. Among the 12 acupuncture sensations in the Massachusetts General Hospital Acupuncture Sensation Scale (MASS), "heaviness" was the strongest and most frequently reported sensation with the 10 mm needles, but not with the 5 mm needles. There were no significant differences in number of sensations elicited, MASS index, range of spreading, and intensity of needle pain for 5 mm penetration versus 1 mm skin press and 10 mm penetration versus 2 mm skin press. The MASS index with 2 mm skin-touch needles was significantly larger than that with 1 mm skin-touch and 5 mm penetrating needles. The factor structures in the 12 acupuncture sensations between penetrating and skin-touch needles were different. The acupuncture sensations obtained in this study under satisfactorily performed double-blind (practitioner-patient) conditions suggest that a slight difference in insertion depth and skin press causes significant differences in quantity and quality of acupuncture sensations.

Passive membrane penetration by ZnO nanoparticles is driven by the interplay of electrostatic and phase boundary conditions.

PubMed

Tiwari, Anuj; Prince, Ashutosh; Arakha, Manoranjan; Jha, Suman; Saleem, Mohammed

2018-02-15

The internalization of nanoparticles through the biological membrane is of immense importance for biomedical applications. A fundamental understanding of the lipid specificity and the role of the membrane biochemical and physical forces at play in modulating penetration are lacking. The current understanding of nanoparticle-membrane interaction is drawn mostly from computational studies and lacks sufficient experimental evidence. Herein, using confocal fluorescence imaging and potentiometric dye-based fluorimetry, we first investigated the interaction of ZnONP in both multi-component and individual lipid membranes using cell-like giant unilamellar vesicles to dissect the lipid specificity; also, we investigated the changes in membrane order, anisotropy and hydrophobicity. ZnONP was found to interact with phosphatidylinositol and phosphatidylcholine head-group-containing lipids specifically. We further investigated the interaction of ZnONP with three physiologically relevant membrane conditions varying in composition and dipole potential. We found that ZnONP interaction leads to a photoinduced enhancement of the partial-to-complete phase separation depending upon the membrane composition and cholesterol content. Interestingly, while the lipid order of a partially-phase-separated membrane remained unchanged upon ZnONP crowding, a fully-phase-separated membrane showed an increase in the lipid order. Strikingly, ZnONP crowding induced a contrasting effect on the fluorescence anisotropy of the membrane upon binding to the two membrane conditions, in line with the measured diffusion coefficient. ZnONP seems to preferentially penetrate through the liquid disordered areas of the membrane and the boundaries of the phase-separated regions driven by the interplay between the electrostatics and phase boundary conditions, which are collectively dictated by the composition and ZnONP-induced lipid reorganization. The results may lead to a greater understanding of the interplay of

How Confocal Is Confocal Raman Microspectroscopy on the Skin? Impact of Microscope Configuration and Sample Preparation on Penetration Depth Profiles.

PubMed

Lunter, Dominique Jasmin

2016-01-01

The aim of the study was to elucidate the effect of sample preparation and microscope configuration on the results of confocal Raman microspectroscopic evaluation of the penetration of a pharmaceutical active into the skin (depth profiling). Pig ear skin and a hydrophilic formulation containing procaine HCl were used as a model system. The formulation was either left on the skin during the measurement, or was wiped off or washed off prior to the analysis. The microscope configuration was varied with respect to objectives and pinholes used. Sample preparation and microscope configuration had a tremendous effect on the results of depth profiling. Regarding sample preparation, the best results could be observed when the formulation was washed off the skin prior to the analysis. Concerning microscope configuration, the use of a 40 × 0.6 numerical aperture (NA) objective in combination with a 25-µm pinhole or a 100 × 1.25 NA objective in combination with a 50-µm pinhole was found to be advantageous. Complete removal of the sample from the skin before the analysis was found to be crucial. A thorough analysis of the suitability of the chosen microscope configuration should be performed before acquiring concentration depth profiles. © 2016 S. Karger AG, Basel.

In vivo investigation of the efficiency of a nanoparticle-emulsion containing polihexanide on the human skin.

PubMed

Ulmer, M; Patzelt, A; Vergou, T; Richter, H; Müller, G; Kramer, A; Sterry, W; Czaika, V; Lademann, J

2013-06-01

Skin antisepsis is a key element for the prevention of surgical site infections, as well as for infections after injection and punctures. Recent investigations have shown that about 25% of the resident bacterial flora of the human skin resides within the hair follicle. These findings strongly suggest that the skin appendages play the role of a bacterial reservoir. The bacteria within the hair follicles therefore may be the cause of endogenous germ repopulation after skin antisepsis, highlighting the need for new antiseptic formulations that can sufficiently penetrate into the hair follicles. Various experiments have found that nano-sized particles as well as oil-in-water emulsions are efficient carriers for substances into the hair follicles. In the present study, we investigated the in vivo antiseptic potential of the particle-associated and aqueous polihexanide on the human skin by monitoring bacterial growth after antisepsis over a period of 2.5h. The experiments suggest that the use of a particle-bound antiseptic can achieve a better and longer lasting antisepsis of the human skin than in non-particulate form. Copyright © 2012 Elsevier B.V. All rights reserved.

[Physicochemical properties and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion].

PubMed

Feng, Ai-Ling; Wang, Ying-Zi; Zhang, Sheng-Hai; Sun, Xiu-Yu; Duan, Fei-Peng; Li, Cai-Xia

2013-08-01

The research aimed at investigating the physicochemical properties, stability and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion. Prepare total alkaloids of S. flavescens nanoemulsion and detect the determination of matrine and oxymatrine in the nanoemulsion using HPLC method. Transmission electron microscopy and laser particle size analyzer were utilized to detect the shape and size of the nanoemulsion respectively. And also the stability of nanoemulsion was studied under the conditions of low temperature (4 degrees C), normal temperature (25 degrees C) and high temperature (60 degrees C). Franz diffusion cell was used to research the transdermal absorption of nanoemulsion in vitro. The results found that the nanoemulsion we prepared presented appearance of rounded, uniform; its average diameter was (15.55 +/- 2.24) nm, and particle size distribution value was 0. 161; the appearance, diameter and percentage determination of total alkaloids of S. flavescens had no variations after 15 d under 4, 25, 60 degrees C respectively. The steady-state permeation rate was 4.564 1 microg x cm(-2) x h(-1), 24 h cumulative amount of penetration was 110.7 microg x cm(-2), which was 1.86 fold of 24 h cumulative amount of aqueous solution (59.41 microg x cm(-2)). All the results demonstrated total alkaloids of S. flavescens nanoemulsion had good permeability, and could provide a new preparation for its clinical application.

Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin.

PubMed

Tran, Ngo Bich Nga Nathalie; Knorr, Fanny; Mak, Wing Cheung; Cheung, Kwan Yee; Richter, Heike; Meinke, Martina; Lademann, Jürgen; Patzelt, Alexa

2017-07-01

Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

The isolated blood-perfused pig ear: an inexpensive and animal-saving model for skin penetration studies.

PubMed

de Lange, J; van Eck, P; Elliott, G R; de Kort, W L; Wolthuis, O L

1992-04-01

To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose consumption and lactate production as metabolic parameters, Na+ and K+ ions, as well as lactate dehydrogenase activity in blood as markers for cell damage, whereas vasomotor reactivity was assessed by administering noradrenaline and isoxsuprine. After 60 min of equilibration, only insignificant changes in these parameters were observed during the subsequent 3-hr test period (longer periods were not tested). A slight weight increase was noted during the total period 4 hr, presumably due to slight edema formation. On the basis of several types of measurements, such as in vivo blood flow and ear temperature and in vitro glucose metabolism, standard procedures were developed. It is concluded that this technique offers an easy to handle, cost-efficient, and animal-saving model for skin penetration studies that lacks most of the disadvantages of existing models.

Mesoporous silica nanoparticles as a promising skin delivery system for methotrexate.

PubMed

Sapino, Simona; Oliaro-Bosso, Simonetta; Zonari, Daniele; Zattoni, Andrea; Ugazio, Elena

2017-09-15

The systemic administration of methotrexate (MTX), a commonly used, antineoplastic drug which is also used in cutaneous disorders, is primarily associated with prolonged retention in the body and consequently with side effects. Innovative drug delivery techniques and alternative administration routes would therefore contribute to its safe and effective use. The general objective of this study is thus the development of MTX-based preparations for the topical treatment of skin disorders. MCM-41-like nanoparticles (MSN), are herein proposed as carriers which can improve the cutaneous absorption and hence the bioavailability and efficacy of MTX. The MTX/MSN complex, prepared via the impregnation procedure, has been physico-chemically characterized, while its cell cultures have had their biocompatibility and bioactivity tested. Furthermore, a series of stable MTX-based dermal formulations has been developed, some containing shea butter, a natural fat. Ex-vivo porcine skin absorption and the transepidermal permeation of MTX have also been monitored in a variety of media using Franz diffusion cells. Interestingly, the epidermal accumulation of the active molecule was increased by its inclusion into MSN, regardless of the surrounding medium. Furthermore, the presence of shea butter enhanced the skin uptake of the drug both in the free and in the loaded form. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy.

PubMed

Su, Yu-Lin; Fang, Jen-Hung; Liao, Chia-Ying; Lin, Chein-Ting; Li, Yun-Ting; Hu, Shang-Hsiu

2015-01-01

A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 °C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf-MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery.

Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy

PubMed Central

Su, Yu-Lin; Fang, Jen-Hung; Liao, Chia-Ying; Lin, Chein-Ting; Li, Yun-Ting; Hu, Shang-Hsiu

2015-01-01

A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 °C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf-MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery. PMID:26379789

Microplasma effect on skin scaffold for melanoma cancer treatment

NASA Astrophysics Data System (ADS)

Abdullah, Zulaika; Zaaba, S. K.; Mustaffa, M. T.; Mohamad, C. W. S. R.; Zakaria, A.

2017-03-01

An atmospheric plasma system using Helium gas was developed. The effect of helium plasma treatment on skin scaffold surface was studied by scanning electron microscopy (SEM). The changes of skin scaffold surfaces before and after helium plasma treatment was recorded. The surface of skin scaffold changed with the prolonged of helium plasma treatment time. The depth of helium plasma penetration was studied using methylene blue dye staining method. The methylene blue will detect the presence or absence of an oxygen that was induced from plasma excitation. The presence of the oxygen indicated on the depth of helium plasma penetration. Results showed plasma are able to penetrate 4mm of skin scaffold after 1200 seconds of exposure.

CREKA peptide-conjugated dendrimer nanoparticles for glioblastoma multiforme delivery.

PubMed

Zhao, Jingjing; Zhang, Bo; Shen, Shun; Chen, Jun; Zhang, Qizhi; Jiang, Xinguo; Pang, Zhiqing

2015-07-15

Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. Nanoparticle diameter can significantly influence the delivery efficiency in tumor tissue. Decreasing nanoparticle size can improve the nanoparticle penetration in tumor tissue but decrease the nanoparticle retention effect. Therefore, small nanoparticles with high retention effect in tumor are urgently needed for effective GBM drug delivery. In present study, a small nanoparticle drug delivery system was developed by conjugating fibrin-binding peptide CREKA to Polyamidoamine (PAMAM) dendrimer, where PEGylated PAMAM is used as drug carrier due to its small size and good penetration in tumor and CREKA is used to target the abundant fibrin in GBM for enhanced retention in tumor. In vitro binding ability tests demonstrated that CREKA can significantly enhanced nanoparticle binding with fibrin. In vivo fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen slices fluorescence imaging further revealed that the CREKA-modified PAMAM achieved higher accumulation and deeper penetration in GBM tissue than unmodified one. These results indicated that the CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy.

PubMed

Ganesan, Palanivel; Choi, Dong-Kug

2016-01-01

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy.

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy

PubMed Central

Ganesan, Palanivel; Choi, Dong-Kug

2016-01-01

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy. PMID:27274231

Effect of a chemical mixture on dermal penetration of arsenic and nickel in male pig in vitro.

PubMed

Turkall, Rita M; Skowronski, Gloria A; Suh, Duck H; Abdel-Rahman, Mohamed S

2003-04-11

The effect of a chemical mixture on the dermal penetration of arsenic or nickel was assessed by applying arsenic-73 or nickel-63 alone or with the chemical mixture to dermatomed male pig skin samples in flow-through diffusion cells. The chemical mixture consisted of chloroform, phenanthrene, and toluene for arsenic penetration studies and phenol, toluene, and trichloroethylene (TCE) for nickel studies. These are predominant chemicals found at hazardous waste sites. Arsenic and nickel bind to skin after dermal exposure. Total penetration of arsenic and nickel in the chemical mixture were significantly increased by 33% and 20% compared to arsenic and nickel alone, respectively. While more radioactivity penetrated skin with chemical treatment than metal alone, significantly less radioactivity was loosely adsorbed to skin and could be easily washed off from the skin surface with soap and water. The results of this study indicate that the potential health risk from dermal exposure to arsenic or nickel is enhanced if other chemicals are present.

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

PubMed

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

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

PubMed

Xie, Wei-Jie; Zhang, Yong-Ping; Xu, Jian; Sun, Xiao-Bo; Yang, Fang-Fang

2017-03-27

In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC 0-t , AUMC 0-t ), area under the zero and first moment curves from 0 to infinity (AUC 0-∞ , AUMC 0-∞ ), maximum plasma concentration (C max ) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3 K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with

Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

2016-10-01

Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies.

Appearance benefits of skin moisturization.

PubMed

Jiang, Z-X; DeLaCruz, J

2011-02-01

Skin hydration is essential for skin health. Moisturized skin is generally regarded as healthy and healthy looking. It is thus speculated that there may be appearance benefits of skin moisturization. This means that there are corresponding changes in the optical properties when skin is moisturized. The appearance of the skin is the result of light reflection, scattering and absorption at various skin layers of the stratum corneum, epidermis, dermis and beyond. The appearance benefits of skin moisturization are likely primarily due to the changes in the optical properties of the stratum corneum. We hypothesize that the major optical effect of skin moisturization is the decrease of light scattering at the skin surface, i.e., the stratum corneum. This decrease of surface scattering corresponds to an increase of light penetration into the deeper layers of the skin. An experiment was conducted to measure the corresponding change in skin spectral reflectance, the skin scattering coefficient and skin translucency with a change in skin hydration. In the experiment, skin hydration was decreased with the topical application of acetone and alcohol and increased with the topical application of known moisturizers and occlusives such as PJ. It was found that both the skin spectral reflectance and the skin scattering coefficient increased when the skin was dehydrated and decreased when the skin was hydrated. Skin translucency increased as the skin became moisturized. The results agree with the hypothesis that there is less light scattering at the skin surface and more light penetration into the deeper skin layers when the skin is moisturized. As a result, the skin appears darker, more pinkish and more translucent. © 2010 John Wiley & Sons A/S.

Radiotherapeutic bandage based on electrospun polyacrylonitrile containing holmium-166 iron garnet nanoparticles for the treatment of skin cancer.

PubMed

Munaweera, Imalka; Levesque-Bishop, Daniel; Shi, Yi; Di Pasqua, Anthony J; Balkus, Kenneth J

2014-12-24

Radiation therapy is used as a primary treatment for inoperable tumors and in patients that cannot or will not undergo surgery. Radioactive holmium-166 ((166)Ho) is a viable candidate for use against skin cancer. Nonradioactive holmium-165 ((165)Ho) iron garnet nanoparticles have been incorporated into a bandage, which, after neutron-activation to (166)Ho, can be applied to a tumor lesion. The (165)Ho iron garnet nanoparticles ((165)HoIG) were synthesized and introduced into polyacrylonitrile (PAN) polymer solutions. The polymer solutions were then electrospun to produce flexible nonwoven bandages, which are stable to neutron-activation. The fiber mats were characterized using scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis and inductively coupled plasma mass spectrometry. The bandages are stable after neutron-activation at a thermal neutron-flux of approximately 3.5 × 10(12) neutrons/cm(2)·s for at least 4 h and 100 °C. Different amounts of radioactivity can be produced by changing the amount of the (165)HoIG nanoparticles inside the bandage and the duration of neutron-activation, which is important for different stages of skin cancer. Furthermore, the radioactive bandage can be easily manipulated to irradiate only the tumor site by cutting the bandage into specific shapes and sizes that cover the tumor prior to neutron-activation. Thus, exposure of healthy cells to high energy β-particles can be avoided. Moreover, there is no leakage of radioactive material after neutron activation, which is critical for safe handling by healthcare professionals treating skin cancer patients.

Green Synthesis of Formulated Zinc Oxide Nanoparticles for Chemical Protection of Skin Care and Related Applications

NASA Astrophysics Data System (ADS)

Koppolu, Ramya

Nanomaterials have diversified applications based on the unique properties. These nanoparticles and functionalized nanocomposites have been studied in the health care filed. Nanoparticles are mostly used in sunscreens which are a part of human life. These sunscreens consist of titanium dioxide and zinc oxide nanoparticles. Due to the higher band crevices, they help the skin to protect from ultraviolet rays, for instance, ultraviolet B and ultraviolet A. A series of nanostructured zinc oxide nanoparticles were prepared by cost-effective chemical and bioinspired methods and variables were optimized. Highly stable and spherical zinc oxide nanoparticles were formulated by aloe vera ( Aloe barbadensis) plant extract and avocado (Persea americana Mill) fruit extract. The state-of-the-art instrumentation was used to characterize the morphology, elemental composition, and particle size distribution. X-ray diffraction data indicated highly crystalline and ultrafine nanoparticles were obtained from the colloidal methods. The X-ray photoelectron spectroscopy results showed the chemical state of zinc, carbon, and oxygen atoms were well-indexed and are used as fingerprint identification of the elements. Transmission electron microscopy images show the shape of particles were cubic and fiber shape contingent upon the protecting operators and heat treatment conditions. The toxicity studies of zinc oxide nanoparticles were found to cause an increase in nitric oxide, which is protecting against further oxidative stress and appears to be nontoxic.

[Effects of penetration enhancers on curcumin transdermal drug delivery].

PubMed

Gao, Zhen-Shen; Wang, Lan; Zhang, Mei

2012-01-01

To study the effects of penetration enhancers and their combinations on the curcumine transdermal drug delivery (CUR-TDDS). The penetration rate of curcumin through rat skin in vitro was measured using Valia-Chien diffusion cells, and orthogonal design method was set up for experimental design. The optimum penetration enhancers were: 3% hydroxypropyl beta cyclodextrins (HP-beta-CD), 9% borneol and 3% peppermint oil. The HP-beta-CD has the most potent enhancing effect.

Effects of chronic alcohol consumption on dermal penetration of pesticides in rats.

PubMed

Brand, R M; Charron, A R; Dutton, L; Gavlik, T L; Mueller, C; Hamel, F G; Chakkalakal, D; Donohue, T M

2004-01-23

Topically applied ethanol is a well-known dermal penetration enhancer. The purpose of this work was to determine if ethanol consumption might also increase transdermal penetration. Male rats were fed either an ethanol containing or control diet for 6-8 wk. After the feeding regime was completed, skin was removed and placed in an in vitro diffusion system. The transdermal absorption of four very commonly used herbicides was determined. Penetration through skin from ethanol-fed rats was enhanced when compared to control by a factor of 5.3 for paraquat, 2.4 for atrazine, and 2.2 for 2,4-dichlorophenoxyacetic acid (2,4-D), and reduced by a factor 0.6 for trifluralin. Comparison of physical factors of the herbicides to the penetration enhancement revealed an inverse linear correlation with lipophilicity, as defined by log octanol/water partition coefficient (log Kow) with r2 =.98. These changes were at least partially reversible after 1 wk of abstinence from ethanol. These experiments demonstrate that regular ethanol consumption can alter the properties of the dermal barrier, leading to increased absorption of some chemicals through rat skin. If ethanol consumption has the same effect on human skin it could potentially have adverse health effects on people regularly exposed to agricultural, environmental, and industrial chemicals.

Pt skin on Pd–Co–Zn/C ternary nanoparticles with enhanced Pt efficiency toward ORR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Weiping; Zhu, Jing; Han, Lili

Exploring highly active, stable and relatively low-cost nanomaterials for the oxygen reduction reaction (ORR) is of vital importance for the commercialization of proton exchange membrane fuel cells (PEMFCs). A highly active, durable, carbon supported, and monolayer Pt coated Pd–Co–Zn nanoparticle is synthesized via a simple impregnation–reduction method, followed by spontaneous displacement of Pt. By tuning the atomic ratios, we obtain the composition–activity volcano curve for the Pd–Co–Zn nanoparticles and determined that Pd : Co : Zn = 8 : 1 : 1 is the optimal composition. Compared with pure Pd/C, the Pd 8CoZn/C nanoparticles show a substantial enhancement in bothmore » the catalytic activity and the durability toward the ORR. Moreover, the durability and activity are further enhanced by forming a Pt skin on Pd 8CoZn/C nanocatalysts. Interestingly, after 10 000 potential cycles in N 2-saturated 0.1 M HClO 4 solution, Pd 8CoZn@Pt/C shows improved mass activity (2.62 A mg -1Pt) and specific activity (4.76 A m -2total), which are about 1.4 and 4.4 times higher than the initial values, and 37.4 and 5.5 times higher than those of Pt/C catalysts, respectively. After accelerated stability testing in O 2-saturated 0.1 M HClO 4 solution for 30 000 potential cycles, the half-wave potential negatively shifts about 6 mV. Our results show that the Pt skin plays an important role in enhancing the activity as well as preventing degradation.« less

Pt skin on Pd–Co–Zn/C ternary nanoparticles with enhanced Pt efficiency toward ORR

DOE PAGES

Xiao, Weiping; Zhu, Jing; Han, Lili; ...

2016-07-15

Exploring highly active, stable and relatively low-cost nanomaterials for the oxygen reduction reaction (ORR) is of vital importance for the commercialization of proton exchange membrane fuel cells (PEMFCs). A highly active, durable, carbon supported, and monolayer Pt coated Pd–Co–Zn nanoparticle is synthesized via a simple impregnation–reduction method, followed by spontaneous displacement of Pt. By tuning the atomic ratios, we obtain the composition–activity volcano curve for the Pd–Co–Zn nanoparticles and determined that Pd : Co : Zn = 8 : 1 : 1 is the optimal composition. Compared with pure Pd/C, the Pd 8CoZn/C nanoparticles show a substantial enhancement in bothmore » the catalytic activity and the durability toward the ORR. Moreover, the durability and activity are further enhanced by forming a Pt skin on Pd 8CoZn/C nanocatalysts. Interestingly, after 10 000 potential cycles in N 2-saturated 0.1 M HClO 4 solution, Pd 8CoZn@Pt/C shows improved mass activity (2.62 A mg -1Pt) and specific activity (4.76 A m -2total), which are about 1.4 and 4.4 times higher than the initial values, and 37.4 and 5.5 times higher than those of Pt/C catalysts, respectively. After accelerated stability testing in O 2-saturated 0.1 M HClO 4 solution for 30 000 potential cycles, the half-wave potential negatively shifts about 6 mV. Our results show that the Pt skin plays an important role in enhancing the activity as well as preventing degradation.« less

Noninvasive penetration of 5 nm hyaluronic acid molecules across the epidermal barrier (in vitro) and its interaction with human skin cells.

PubMed

Nashchekina, Yu A; Raydan, M

2018-02-01

Hyaluronic acid represents one of the major components of the extracellular environment. The main challenge remains in the ability to deliver these molecules noninvasively across the skin barrier, which can be overcome by the reduction in size to an extent that allows these molecules to pass across the skin barrier. The aim of this study was to measure the penetration and bioavailability of low molecular weight hyaluronic acid to cross an epidermal barrier model. Determining the quantity of hyaluronic acid in the test solutions was carried with method of photocolorimetry analysis. Investigation of the interaction of cells with LMWHA was studied with a confocal microscope. The study showed that LMWHA is able to cross the epidermis. Most effective penetration level is during the first 6 hours reaching 75%, and then the concentration started to decline and reached the equilibrium state within the following 2 hours. Confocal laser microscopy demonstrated different distribution and behavior of these molecules among the keratinocytes and fibroblasts. Reducing the size of hyaluronic acid to 5 nm enhance their transport across the epidermal layer. The concentration of hyaluronic acid molecules was higher on the fibroblast surface in comparison to their extracellular environment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis of sub-10 nm solid lipid nanoparticles for topical and biomarker detection applications

NASA Astrophysics Data System (ADS)

Calderón-Colón, Xiomara; Patchan, Marcia W.; Theodore, Mellisa L.; Le, Huong T.; Sample, Jennifer L.; Benkoski, Jason J.; Patrone, Julia B.

2014-02-01

Solid lipid nanoparticles (SLNs) are a promising platform for sensing in vivo biomarkers due to their biocompatibility, stability, and their ability to carry a wide range of active ingredients. The skin is a prominent target organ for numerous inflammatory and stress-related biomarkers, making it an excellent site for early detection of physiological imbalance and application of sensory nanoparticles. Though smaller particle size has generally been correlated with increased penetration of skin models, there has been little attention paid to the significance of other nanoparticle synthesis parameters with respect to their physical properties. In this study, we demonstrate the synthesis of sub-10 nm SLNs by the phase inversion temperature (PIT) method. These particles were specifically designed for topical delivery of hydrogen peroxide-detecting chemiluminescent dyes. A systematic design of experiments approach was used to investigate the role of the processing variables on SLN form and properties. The processing variables were correlated with the SLN properties (e.g., dye solubility, phase inversion temperature, particle size, polydispersity, melting point, and latent heat of melting). Statistical analysis revealed that the PIT method, while allowing total control over the thermal properties, resulted in well-controlled synthesis of ultra-small particles, while allowing great flexibility in the processing conditions and incorporated compounds.

A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine.

PubMed

Taghizadeh, S Mojtaba; Moghimi-Ardakani, Ali; Mohamadnia, Fatemeh

2015-03-01

A series of drug-in-adhesive transdermal drug delivery systems (patch) with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box-Behnken experimental design. The response surface methodology based on a three-level, three-variable Box-Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0-8% of each chemical penetration enhancer). Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm(2) h) was higher than Tween 80 (1.473 μg/cm(2) h) and lauryl alcohol (0.843 μg/cm(2) h), and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt) enhancers exhibited the highest efficiency.

Sub-40 fs, 1060-nm Yb-fiber laser enhances penetration depth in nonlinear optical microscopy of human skin

NASA Astrophysics Data System (ADS)

Balu, Mihaela; Saytashev, Ilyas; Hou, Jue; Dantus, Marcos; Tromberg, Bruce J.

2015-12-01

Advancing the practical utility of nonlinear optical microscopy requires continued improvement in imaging depth and contrast. We evaluated second-harmonic generation (SHG) and third-harmonic generation images from ex vivo human skin and showed that a sub-40 fs, 1060-nm Yb-fiber laser can enhance SHG penetration depth by up to 80% compared to a >100 fs, 800 nm Ti:sapphire source. These results demonstrate the potential of fiber-based laser systems to address a key performance limitation related to nonlinear optical microscopy (NLOM) technology while providing a low-barrier-to-access alternative to Ti:sapphire sources that could help accelerate the movement of NLOM into clinical practice.

What determines skin sensitization potency: Myths, maybes ...

EPA Pesticide Factsheets

It is widely considered to be a self-evident truth that substances must have a molecular weight (MW) less than 500 to effectively penetrate through the skin in order to induce sensitisation. However, Roberts et al. 2010, evaluated a data set of 699 substances taken from the TIMES-SS expert system and identified that of the 13 substances with a MW above 500, 5 were reported as skin sensitisers. This provided good evidence to refute such a MW threshold. The present study set about compiling a larger and more diverse set of substances such as those evaluated for their skin sensitisation potential under the EU REACH regulation. A dataset of 2575 substances that had been tested for skin sensitisation, using guinea pigs and/or mice was collected. The dataset contained 197 substances with a MW>500: 33 of these were categorised as skin sensitisers. Each of the 33 substances were then evaluated in turn – metal containing complexes, reaction products and mixtures were excluded from further consideration. The final set of 14 sensitisers with a MW>500 were considered on the basis of their reaction chemistry to propose likely mechanistic explanations for their sensitisation behaviour. Penetration ability is correlated with MW (and LogKow): if the MW threshold is shown to be inapplicable for skin sensitisation potency, in turn it also indicates that penetration is not a relevant parameter for skin sensitisation. Exercise to search and extract REACH data for the skin se

Penetration studies of an extremely lipophilic active model substance from an oil-in-water emulsion: influence of the lipophilicity of the formulation in human skin - part 2.

PubMed

Naumann, S; Lange, S; Polak, G; Kalhoelfer, V; Motlagh, L; Goebel, A; Wohlrab, J; Neubert, R H H

2014-01-01

The effect of the lipophilicity of a carrier on human skin penetration of an extremely lipophilic active model substance was evaluated by using Franz type diffusion cells. Oil-in-water model emulsions containing different amounts of the oily phase were prepared, and Myritol® PC (M-PC) was selected as lipophilic marker component of the oily phase. The penetrated amounts of the lipophilic model substance salicyloyl phytosphingosine (SP) were determined by high-performance liquid chromatography with ultraviolet detection, while M-PC was detected using gas chromatography coupled with mass spectrometry. It has been ascertained that the amount of the lipid phase within the emulsion influenced the penetration profile of the active ingredient SP. The emulsion containing the lowest proportion of the lipid phase provides the best conditions for SP penetration. Surprisingly, the penetration behavior of M-PC was influenced by the oily phase in the same way. Regarding the M-PC and the SP penetration profiles from each emulsion, a solvent drag mechanism can be assumed whereby M-PC acts as penetration enhancer. In conclusion, the penetration rate of the active ingredient SP and the marker component M-PC are in reverse proportion to the oil content of the formulations. The lipophilicity of SP and M-PC, their solubility and their thermodynamic activity within the vehicle could have an effect on their penetration behavior. Additionally, M-PC has the property to enhance the penetration rates of extremely lipophilic substances even at low concentrations.

Skin Dendritic Cell Targeting via Microneedle Arrays Laden with Antigen-Encapsulated Poly-d,l-lactide-co-Glycolide Nanoparticles Induces Efficient Antitumor and Antiviral Immune Responses

PubMed Central

2013-01-01

The efficacious delivery of antigens to antigen-presenting cells (APCs), in particular, to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC networks within the skin. Following in situ uptake, skin-resident DCs were able to deliver antigen-encapsulated poly-d,l-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen-encapsulated nanoparticle vaccination via microneedles generated robust antigen-specific cellular immune responses in mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8+ T cells that resulted in efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage. PMID:23373658

Forces required for a knife to penetrate a variety of clothing types.

PubMed

Nolan, Gary; Hainsworth, Sarah V; Rutty, Guy N

2013-03-01

In stabbing incidents, it is usual for the victim to be clothed and therefore a knife penetrates both clothes and skin. Clothes (other than leather) have been thought to make little difference to the penetration force. However, there is little quantitative data in the literature. In this study, a range of clothes have been tested, either singly or in layers of, for example, T-shirt and shirt, to quantify the additional force required when clothes are present. A materials testing system has been used to test the penetration force required to stab through clothes into a foam-silicone rubber skin simulant. The results show that the force required can be significantly different, particularly when layers of clothing are penetrated. A cotton t-shirt adds c. 8 N to the penetration force, while a T-shirt and jacket can add an additional 21 N. The results allow a more quantitative assessment of forces required in stabbing. © 2012 American Academy of Forensic Sciences.

A cyclohexanecarboxamide derivative with inhibitory effects on Schistosoma mansoni cercarial serine protease and penetration of mice skin by the parasite.

PubMed

Bahgat, Mahmoud; Aboul-Enein, Mohamed N; El Azzouny, Aida A; Maghraby, Amany; Ruppel, Andreas; Soliman, Wael M

2009-01-01

A cyclohexanecarboxamide derivative, N-phenyl-N-[1-(piperidine-1-carbonyl)cyclohexyl] benzamide (MNRC-5), was evaluated for its inhibitory effects on Schistosoma mansoni cercarial serine protease activity and cercarial penetration. MNRC-5 exerted an inhibitory effect on S. mansoni cercarial serine protease at serial concentrations of the specific chromogenic substrate Boc-Val-Leu-Gly-Arg-PNA for such enzyme family and the inhibitory coefficient (Ki) value was deduced. Moreover, topical treatment of mice tails with the most potent inhibitory concentration of MNRC-5 formulated in jojoba oil successfully blocked cercarial penetration as demonstrated by a significant reduction (75%; p < 0.05) in the recovered S. mansoni worms from treated mice in comparison to control ones whose tails were painted with jojoba oil base containing no MNRC-5. In addition, the IgM and IgG reactivities to crude S. mansoni cercarial, worm and egg antigens were generally lower in sera from treated infected mice than untreated infected mice. In conclusion, we report on a new serine protease inhibitor capable for blocking penetration of host skin by S. mansoni cercariae as measured by lowering worm burden and decrease in the levels of both IgM and IgG towards different bilharzial antigens upon topical treatment.

Effect of 1,4-cyclohexanediol on percutaneous absorption and penetration of azelaic acid.

PubMed

Li, Nan; Su, Qian; Tan, Fengping; Zhang, Jerry

2010-03-15

The objective of this study is to investigate the effect of 1,4-cyclohexanediol as a retardant on the percutaneous absorption and penetration of azelaic acid. Hairless rat skin was mounted on Franz diffusion cells and treated with topical formulations containing solubilized azelaic acid with and without 1,4-cyclohexanediol. The skin was separated into stratum corneum and the deeper skin layers. The azelaic acid collected in receptor medium and each layer at the end of each time point was extracted and quantified. A significant decrease in flux across the skin suggests a penetration retardation effect of 1,4-cyclohexanediol (42.50 microg/cm(2)/h in the presence of vs. 76.25 microg/cm(2)/h in the absence of) at active loading level of 1.13 mg/cm(2). The penetration retardation effect was also observed at higher active loading level (2.82 mg/cm(2)). Furthermore, presence of 1,4-cyclohexanediol in the topical formulation did not reduce the skin and epidermal retention of azelaic acid, suggesting its potential use in the development of superior topical formation for reducing potential systematic side effect while maintaining therapeutic efficiency. 2009 Elsevier B.V. All rights reserved.

Construction of new skin models and calculation of skin dose coefficients for electron exposures

NASA Astrophysics Data System (ADS)

Yeom, Yeon Soo; Kim, Chan Hyeong; Nguyen, Thang Tat; Choi, Chansoo; Han, Min Cheol; Jeong, Jong Hwi

2016-08-01

The voxel-type reference phantoms of the International Commission on Radiological Protection (ICRP), due to their limited voxel resolutions, cannot represent the 50- μm-thick radiosensitive target layer of the skin necessary for skin dose calculations. Alternatively, in ICRP Publication 116, the dose coefficients (DCs) for the skin were calculated approximately, averaging absorbed dose over the entire skin depth of the ICRP phantoms. This approximation is valid for highly-penetrating radiations such as photons and neutrons, but not for weakly penetrating radiations like electrons due to the high gradient in the dose distribution in the skin. To address the limitation, the present study introduces skin polygon-mesh (PM) models, which have been produced by converting the skin models of the ICRP voxel phantoms to a high-quality PM format and adding a 50- μm-thick radiosensitive target layer into the skin models. Then, the constructed skin PM models were implemented in the Geant4 Monte Carlo code to calculate the skin DCs for external exposures of electrons. The calculated values were then compared with the skin DCs of the ICRP Publication 116. The results of the present study show that for high-energy electrons (≥ 1 MeV), the ICRP-116 skin DCs are, indeed, in good agreement with the skin DCs calculated in the present study. For low-energy electrons (< 1 MeV), however, significant discrepancies were observed, and the ICRP-116 skin DCs underestimated the skin dose as much as 15 times for some energies. Besides, regardless of the small tissue weighting factor of the skin ( w T = 0.01), the discrepancies in the skin dose were found to result in significant discrepancies in the effective dose, demonstarting that the effective DCs in ICRP-116 are not reliable for external exposure to electrons.

Results of analyses performed on soil adjacent to penetrators emplaced into sediments at McCook, Nebraska, January 1976. [simulated penetration into wind-deposited sediments on Martian plains

NASA Technical Reports Server (NTRS)

Blanchard, M.; Bunch, T.; Davis, A.; Kyte, F.; Shade, H.; Erlichman, J.; Polkowski, G.

1977-01-01

During 1976 several penetrators (full and 0.58 scale) were dropped into a test site McCook, Nebraska. The McCook site was selected because it simulated penetration into wind-deposited sediments (silts and sands) on Martian plains. The physical and chemical modifications found in the sediment after the penetrators' impact are described. Laboratory analyses have shown mineralogical and elemental changes are produced in the sediment next to the penetrator. Optical microscopy studies of material next to the skin of the penetrator revealed a layer of glassy material about 75 microns thick. Elemental analysis of a 0-1-mm layer of sediment next to the penetrator revealed increased concentrations for Cr, Fe, Ni, Mo, and reduced concentrations for Mg, Al Si, P, K, and Ca. The Cr, Fe, Ni, and Mo were in fragments abraded from the penetrator. Mineralogical changes occurring in the sediment next to the penetrator included the introduction of micron-size grains of alpha iron and several hydrated iron oxide minerals. The newly formed silicate minerals include metastable phases of silica (cristobalite, lechatelierite, and opal). The glassy material was mostly opal which formed when the host minerals (mica, calcite, and clay) decomposed. In summary, contaminants introduced by the penetrator occur up to 2 mm away from the penetrator's skin. Although volatile elements do migrate and new minerals are formed during the destruction of host minerals in the sediment, no changes were observed beyond the 2-mm distance. The analyses indicate 0.58-scale penetrators do effectively simulate full-scale testing for soil modification effects.

Distribution and Biological Effects of Nanoparticles in the Reproductive System.

PubMed

Liu, Ying; Li, Hongxia; Xiao, Kai

2016-01-01

Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our

A dual strategy to improve the penetration and treatment of breast cancer by combining shrinking nanoparticles with collagen depletion by losartan.

PubMed

Cun, Xingli; Ruan, Shaobo; Chen, Jiantao; Zhang, Li; Li, Jianping; He, Qin; Gao, Huile

2016-02-01

Although development of nanomedicines has been a promising direction in tumor treatment, the therapeutic outcome of current nanomedicines is unsatisfying, partly because of the poor retention and penetration in tumors. Recently, a kind of tumor microenvironment sensitive size shrinkable nanoparticles (DOX-AuNPs-GNPs) has been developed by our lab, which could enhance the tumor penetration and retention depending on the size shrinking. However, the further enhancement is still restricted by dense collagen network in tumors. Thus in this study, we combined DOX-AuNPs-GNPs with losartan to deplete tumor collagen (constituted up to 90% of extracellular matrix) to further improve tumor penetration. In vitro, DOX-AuNPs-GNPs can shrink from over 117.8nm to less than 50.0nm and release DOX-AuNPs under the triggering of tumor overexpressed matrix metalloproteinases-2 (MMP-2). In vivo, pretreatment with losartan significantly decrease the collagen level and improve the tumor penetration. In combination, losartan combined with DOX-AuNPs-GNPs showed the best drug delivery efficiency, striking penetration efficiency and best 4T1 breast tumor inhibition effect. In conclusion, this study provided a promising synergetic strategy to improve the tumor treatment efficiency of nanomedicines. We have developed a dual strategy for deep tumor penetration through combining size shrinkable DOX-AuNPs-GNPs with depleting tumor collagen by losartan. Additionally, we demonstrate therapeutic efficacy in breast tumor bearing mouse model. DOX-AuNPs-GNPs co-administration with losartan is a novel and highly attractive strategy for anti-tumor drug delivery with the potential for broad applications in clinic. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An in vivo confocal Raman study of the delivery of trans retinol to the skin.

PubMed

Pudney, Paul D A; Mélot, Mickaël; Caspers, Peter J; Van Der Pol, Andre; Puppels, Gerwin J

2007-08-01

The purpose of this study is to monitor in vivo the delivery of trans-retinol into human skin. Delivery to real systems, such as skin, can be extremely difficult to execute and is problematic to confirm and measure. So far, methods for studying the delivery of compounds through the skin are mostly ex vivo and so inherently influence the skin and may not translate directly to the in vivo situation. Raman spectroscopy is uniquely placed to be able to measure biological processes in vivo, and this paper shows that the trans-retinol penetration into the skin can successfully be measured in vivo using this technique. This study measured the volar forearm of volunteers treated with 0.3% trans-retinol in propylene glycol (PG)/ethanol and 0.3% trans-retinol in caprylic/capric acid triglyceride (MYRITOL318), an oil found in skin creams. Solutions were applied and then confocal Raman depth profiles were obtained of the stratum corneum (SC) and into the viable epidermis (VE) up to 10 hours after treatment. Remarkable differences between a penetrating and a nonpenetrating solution can clearly be observed. Treating with trans-retinol in PG/ethanol results in trans-retinol penetrating through the SC and into the VE. Its penetration was also observed to be highly correlated with the depth of penetration of the PG, which is well known as an efficient penetration enhancer. In contrast, while treating with trans-retinol in MYRITOL318, trans-retinol hardly penetrates at all. For the first time, the penetration of trans-retinol has been monitored directly after application of solutions, in vivo without skin excision. Here, the effect of two different solutions on the delivery of trans-retinol into the skin was measured very effectively in vivo by Raman spectroscopy.

Penetration depth, concentration and efficiency of transdermal α-arbutin delivery after ultrasound treatment with albumin-shelled microbubbles in mice.

PubMed

Liao, Ai-Ho; Ma, Wan-Chun; Wang, Chih-Hung; Yeh, Ming-Kung

2016-09-01

Recently, the feasibility and effects of using microbubbles (MBs) as an ultrasound (US) contrast agent for enhancing the penetration in transdermal delivery in vivo have been demonstrated, but the mechanism and efficiency are unclear. This study demonstrates the penetration depth, concentration and efficiency of transdermal α-arbutin delivery during 4 weeks after US treatment with MBs in mice. Experimental animals were randomly divided into the following four groups (n = 5 animals per group): (1) penetrating α-arbutin alone (C), (2) US combined with penetrating α-arbutin, (3) US combined with MBs and penetrating α-arbutin, and (4) US combined with diluted MBs and penetrating α-arbutin (UBD). The penetration depths in agarose phantoms and pigskin were 47 and 84% greater for group UBD, respectively, than for group C. The in vitro skin penetration by 2% α-arbutin after 3 h was 83% greater in group UBD than in group C. The degree of in vivo skin whitening (quantified as the luminosity index) in group UBD significantly increased by 25% after 1 week, 34% after 2 weeks, and then stabilized after 3 weeks at 37% in C57BL/6J mice over a 4-week experimental period. Our results indicate that combined treatment with optimal US and MBs can increase skin permeability so as to enhance α-arbutin delivery to inhibit melanogenesis without damaging the skin in mice.

Development of terbinafine solid lipid nanoparticles as a topical delivery system

PubMed Central

Chen, Ying-Chen; Liu, Der-Zen; Liu, Jun-Jen; Chang, Tsung-Wei; Ho, Hsiu-O; Sheu, Ming-Thau

2012-01-01

To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a <5% lipid phase and >50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® Once™, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™. PMID:22923986

Enhanced and selective permeability of gold nanoparticles functionalized with cell penetrating peptide derived from maurocalcine animal toxin.

PubMed

Khamehchian, Sedigheh; Nikkhah, Maryam; Madani, Rasool; Hosseinkhani, Saman

2016-11-01

Functionalization of gold nanoparticles (GNPs) is suitable for many applications such as biomedical imaging, clinical diagnosis, and targeted delivery by conjugating cell-penetrating peptides (CPPs). Here, we investigated intracellular uptake of GNP conjugated to MCaUF1-9(Ala) , a CPP derived from maurocalcine (MCa) animal toxin, and compared it with TAT functionalized GNP. Peptide conjugated GNP was characterized using UV-Visible spectroscopy, dynamic light scattering, zeta potential, and transmission electron microscopy. Uptake of MCaUF1-9(Ala) and TAT functionalized GNPs was evaluated in three cell lines, HeLa, MDA-MB-231, and A431, using dark field imaging and atomic absorption spectroscopy. According to peptide sequences and type of cells different cell penetrating activity was observed. Peptide functionalized GNP had little effect on cell viability and respect to net charge difference between peptide, showed interesting selectivity against three cell types. Peptide conjugated to GNPs displayed higher uptake than bare GNPs in the all cell lines except HeLa cell with lowest internalization. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2693-2700, 2016. © 2016 Wiley Periodicals, Inc.

Delivery and reveal of localization of upconversion luminescent microparticles and quantum dots in the skin in vivo by fractional laser microablation, multimodal imaging, and optical clearing

NASA Astrophysics Data System (ADS)

Volkova, Elena K.; Yanina, Irina Yu; Genina, Elina A.; Bashkatov, Alexey N.; Konyukhova, Julia G.; Popov, Alexey P.; Speranskaya, Elena S.; Bucharskaya, Alla B.; Navolokin, Nikita A.; Goryacheva, Irina Yu.; Kochubey, Vyacheslav I.; Sukhorukov, Gleb B.; Meglinski, Igor V.; Tuchin, Valery V.

2018-02-01

Delivery and spatial localization of upconversion luminescent microparticles [Y2O3:Yb, Er] (mean size ˜1.6 μm) and quantum dots (QDs) (CuInS2/ZnS nanoparticles coated with polyethylene glycol-based amphiphilic polymer, mean size ˜20 nm) inside rat skin was studied in vivo using a multimodal optical imaging approach. The particles were embedded into the skin dermis to the depth from 300 to 500 μm through microchannels performed by fractional laser microablation. Low-frequency ultrasound was applied to enhance penetration of the particles into the skin. Visualization of the particles was revealed using a combination of luminescent spectroscopy, optical coherence tomography, confocal microscopy, and histochemical analysis. Optical clearing was used to enhance the image contrast of the luminescent signal from the particles. It was demonstrated that the penetration depth of particles depends on their size, resulting in a different detection time interval (days) of the luminescent signal from microparticles and QDs inside the rat skin in vivo. We show that luminescent signal from the upconversion microparticles and QDs was detected after the particle delivery into the rat skin in vivo during eighth and fourth days, respectively. We hypothesize that the upconversion microparticles have created a long-time depot localized in the laser-created channels, as the QDs spread over the surrounding tissues.

Fire extinguishing apparatus having a slidable mass for a penetrator nozzle. [for penetrating aircraft and shuttle orbiter skin

NASA Technical Reports Server (NTRS)

Gray, N. C.; Senseny, R. M.; Bolton, P. N.

1980-01-01

A fire extinguishing apparatus for delivering an extinguishing agent through a tarrier surrounding a structure into its interior includes an elongated tubular nozzle body which has a pointed penetrating head carried on one end of the tubular body. A source of extinguishing agent coupled to the opposite end of the tubular body is fed through and passes through passages adjacent the head for delivering the extinguishing agent to the interior of the structure. A slidable mass is carried on the tubular body on a remote end of the tubular body from the penetrating head. By manipulating the slidable mass and bringing such in contact with an abutment the force imparted to the tubular body causes the head to penetrate the structure.

Assessment of the in vitro dermal irritation potential of cerium, silver, and titanium nanoparticles in a human skin equivalent model

EPA Science Inventory

AbstractDermal exposure to metals may res·ult in irritant contact dermatitis. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from epidermal keratinocytes. These cultured cells form a m...

Vehicle and enhancer effects on human skin penetration of aminophylline from cream formulations: evaluation in vivo.

PubMed

Wang, Lai-Hao; Wang, Chia-Chen; Kuo, Su-Ching

2007-01-01

The effects of four essential oils (rosemary, ylang, lilacin, and peppermint oils), and three plant oils (jojoba oil, corn germ oil, and olive oil) on the permeation of aminophylline were studied using human skin. The permeation effects of these oils were compared with those of three chemical penetration enhancers. Although all oils enhanced the permeation of aminophylline, their effects were less than that of ethanol. Jojoba oil was found to be the most active, causing about a 32% peak height decrease of N-H bending absorbances in comparison with the control, while peppermint, lilacin, rosemary, and ylang oils caused 28%, 24%, 18%, and 12% peak height decreases, respectively. Microemulsions containing 10% jojoba oil and 30% corn germ oil were found to be superior vehicles for the percutaneous absorption of aminophylline. Comparision with results obtained from high-performance liquid chromatography shows good agreement.

Ex vivo skin absorption of terpenes from Vicks VapoRub ointment.

PubMed

Cal, Krzysztof; Sopala, Monika

2008-08-01

The pharmaceutical market offers a wide range of inhalant drug products applied on the skin that contain essential oils and/or their isolated compounds, i.e. terpenes. Because there are few data concerning the skin penetration of terpenes, especially from complex carriers, the goal of this study was to determine the ex vivo skin absorption kinetics of chosen terpenes, namely eucalyptol, menthol, camphor, alpha-pinene, and beta-pinene, from the product Vicks VapoRub. Human cadaver skin was placed in a flow-through diffusion chamber and the product was applied for 15, 30, and 60 min. After the application time the skin was separated into layers using a tape-stripping technique: three fractions of stratum corneum and epidermis with dermis, and terpenes amounts in the samples were determined by gas-chromatography. The investigated terpenes showed different absorption characteristics related to their physicochemical properties and did not permeate through the skin into the acceptor fluid. Eucalyptol had the largest total accumulation in the stratum corneum and in the epidermis with dermis, while alpha-pinene penetrated into the skin in the smallest amount. The short time in which saturation of the stratum corneum with the terpenes occurred and the high accumulation of most of the investigated terpenes in the skin layers proved that these compounds easily penetrate and permeate the stratum corneum and that in vivo they may easily penetrate into the blood circulation.

Can the Hydroxyapatite-Coated Skin-Penetrating Abutment for Bone Conduction Hearing Implants Integrate with the Surrounding Skin?

PubMed

van Hoof, Marc; Wigren, Stina; Duimel, Hans; Savelkoul, Paul H M; Flynn, Mark; Stokroos, Robert Jan

2015-01-01

Percutaneous implants, such as bone conduction hearing implants, suffer from complications that include inflammation of the surrounding skin. A sealed skin-abutment interface can prevent the ingress of bacteria, which should reduce the occurrence of peri-abutment dermatitis. It was hypothesized that a hydroxyapatite (HA)-coated abutment in conjunction with soft tissue preservation surgery should enable integration with the adjacent skin. Previous research has confirmed that integration is never achieved with as-machined titanium abutments. Here, we investigate, in vivo, if skin integration is achievable in patients using a HA-coated abutment. One titanium abutment (control) and one HA-coated abutment (case) together with the surrounding skin were surgically retrieved from two patients who had a medical indication for this procedure. Histological sections of the skin were investigated using light microscopy. The abutment was qualitatively analyzed using scanning electron microscopy. The titanium abutment only had a partial and thin layer of attached amorphous biological material. The HA-coated abutment was almost fully covered by a pronounced thick layer of organized skin, composed of different interconnected structural layers. Proof-of-principle evidence that the HA-coated abutment can achieve integration with the surrounding skin was presented for the first time.

Antibacterial activity of silver nanoparticle-coated fabric and leather against odor and skin infection causing bacteria.

PubMed

Velmurugan, Palanivel; Lee, Sang-Myeong; Cho, Min; Park, Jung-Hee; Seo, Sang-Ki; Myung, Hyun; Bang, Keuk-Soo; Oh, Byung-Taek

2014-10-01

We present a simple, eco-friendly synthesis of silver and gold nanoparticles using a natural polymer pine gum solution as the reducing and capping agent. The pine gum solution was combined with silver nitrate (AgNO3) or a chloroauric acid (HAuCl4) solution to produce silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), respectively. The reaction process was simple; formation of the nanoparticles was achieved by autoclaving the silver and gold ions with the pine gum. UV-Vis spectra showed surface plasmon resonance (SPR) for silver and gold nanoparticles at 432 and 539 nm, respectively. The elemental forms of AgNPs and AuNPs were confirmed by energy-dispersive X-ray spectroscopy (EDX). Fourier transform infrared spectroscopy (FTIR) showed the biomolecules present in the pine gum, AgNPs, and AuNPs. Transmission electron microscopy (TEM) images showed the shape and size of AgNPs and AuNPs. The crystalline nature of synthesized AgNPs and AuNPs was confirmed by X-ray crystallography [X-ray diffraction (XRD)]. Application of synthesized AgNPs onto cotton fabrics and leather, in order to evaluate their antibacterial properties against odor- or skin infection-causing bacteria, is also discussed. Among the four tested bacteria, AgNP-coated cotton fabric and leather samples displayed excellent antibacterial activity against Brevibacterium linens.

The skin reservoir of sulphur mustard.

PubMed

Hattersley, I J; Jenner, J; Dalton, C; Chilcott, R P; Graham, J S

2008-09-01

Studies of the percutaneous reservoir of sulphur mustard (HD) formed during absorption carried out during WWI and WWII are inconclusive. More recent studies have indicated that a significant amount of unreacted HD remains in human epidermal membranes during percutaneous penetration studies in vitro. The present study investigated the nature and persistence of the HD reservoir formed during in vitro penetration studies using dermatomed slices of human and pig skin (0.5mm thick). Amounts of (14)C-HD that (a) penetrated, (b) remained on the surface, (c) were extractable from and (d) remained in the skin after extraction were estimated by liquid scintillation counting (confirmed using GC-MS analysis). The results demonstrated that there is a reservoir of HD in human and pig skin for up to 24 h after contamination of the skin surface in vitro with liquid agent. At least some of this reservoir could be extracted with acetonitrile, and the amounts of extracted and unextracted HD exceed the amount required to produce injury in vivo by at least 20 fold. The study demonstrated the presence of a reservoir whether the skin was covered (occluded) or left open to the air (unoccluded). The study concluded that the extractable reservoir was significant in terms of the amount of HD required to induce a vesicant response in human skin. The extractable reservoir was at least 20 times the amount required per cm(2) estimated to cause a response in all of the human population, as defined by studies carried out in human volunteers during the 1940s.

ZnO nanoparticles and organic chemical UV-filters are equally well tolerated by human immune cells.

PubMed

O'Keefe, Sean J; Feltis, Bryce N; Piva, Terrence J; Turney, Terence W; Wright, Paul F A

2016-11-01

An important part of assessing the toxic potential of nanoparticles for specific applications should be the direct comparison of biological activities with those of alternative materials for the same application. Nanoparticulate inorganic ultraviolet (UV) filters, such as zinc oxide (ZnO), are commonly incorporated into transparent sunscreen and cosmetic formulations. However, concerns have been raised about potential unwanted effects, despite their negligible skin penetration and inherent advantages over organic chemical UV-filters. To provide useful application-relevant assessments of their potential hazard with/without UVA co-exposure, we directly compared cytotoxic and immune response profiles of human THP-1 monocytic cells to ZnO nanoparticles (30 nm) with bulk ZnO particulates (200 nm) and five conventional organic chemical UV-filters - butylmethoxydibenzoylmethane (avobenzone), octylmethoxycinnamate, octylsalicylate, homosalate and 4-methylbenzylidene camphor. High exposure concentrations of both organic and particulate UV-filters were required to cause cytotoxicity in monocyte and macrophage cultures after 24 h. Co-exposure with UVA (6.7 J/cm(2)) did not alter cytotoxicity profiles. Particle surface area-based dose responses showed that ZnO NPs were better tolerated than bulk ZnO. Organic and particulate UV-filters increased apoptosis at similar doses. Only particulates increased the generation of reactive oxygen species. Interleukin-8 (IL-8) release was increased by all particulates, avobenzone, homosalate and octylsalicylate. IL-1β release was only increased in macrophages by exposure to avobenzone and homosalate. In conclusion, direct effects were caused in monocytes and macrophages at similar concentrations of both organic UV-filters and ZnO nanoparticulates - indicating that their intrinsic cytotoxicity is similar. With their lower skin penetration, ZnO nanoparticles are expected to have lower bioactivity when used in sunscreens.

Design, Synthesis of Novel Lipids as Chemical Permeation Enhancers and Development of Nanoparticle System for Transdermal Drug Delivery

PubMed Central

Shah, Punit P.; Etukala, Jagan Reddy; Vemuri, Adithi; Singh, Mandip

2013-01-01

In the present study, we designed and developed novel lipids that include (Z)-1-(Octadec-9-en-1-yl)-pyrrolidine (Cy5T), 1, 1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin-1-ium iodide (Cy5), (Z)-1-(Octadec-9-en-1-yl)-piperidine (Cy6T), and 1, 1-Di-((Z)-octadec-9-en-1-yl) piperidin-1-ium iodide (Cy6) to enhance the transdermal permeation of some selected drugs. Firstly, we evaluated the transdermal permeation efficacies of these lipids as chemical permeation enhancers in vehicle formulations for melatonin, ß-estradiol, caffeine, α-MSH, and spantide using franz diffusion cells. Among them Cy5 lipid was determined to be the most efficient by increasing the transdermal permeation of melatonin, ß-estradiol, caffeine, α-MSH, and spantide by 1.5 to 3.26-fold more at the epidermal layer and 1.3 to 2.5-fold more at the dermal layer, in comparison to either NMP or OA. Hence we developed a nanoparticle system (cy5 lipid ethanol drug nanoparticles) to evaluate any further improvement in the drug penetration. Cy5 lipid formed uniformly sized nanoparticles ranging from 150–200 nm depending on the type of drug. Further, Cy5 based nanoparticle system significantly (p<0.05) increased the permeation of all the drugs in comparison to the lipid solution and standard permeation enhancers. There were about 1.54 to 22-fold more of drug retained in the dermis for the Cy5 based nanoparticles compared to OA/NMP standard enhancers and 3.87 to 66.67-fold more than lipid solution. In addition, epifluorescent microscopic analysis in rhodamine-PE permeation studies confirmed the superior permeation enhancement of LEDs (detection of fluorescence up to skin depth of 340 μm) more than lipid solution, which revealed fluorescence up to skin depth of only 260 μm. In summary the present findings demonstrate that i) cationic lipid with 5 membered amine heterocyclic ring has higher permeating efficacy than the 6 membered amine hertocyclic ring. ii) The nanoparticle system prepared with Cy5 showed

Penetration of theophylline and adenosine into excised human skin from binary and ternary vehicles: effect of a nonionic surfactant.

PubMed

Kadir, R; Stempler, D; Liron, Z; Cohen, S

1989-02-01

A nonionic surfactant, diethyleneglycol lauryl ether (PEG-2-L), increases the flux of either theophylline or adenosine by a factor of 2.2-2.7, when these are delivered from propionic acid solutions into human skin samples, with respect to propionic acid alone. At the same time, the flux of propionic acid from the same vehicles is decreased. Significant expansion of the partial molal volumes vi of both purines occurs following incorporation of PEG-2-L into their propionic acid solution. Hence, the enhancing effect of this surfactant arises mainly from an increase in the excess free energy of these solutes in the donor phase ("push" effect). Paraffin oil increases the flux of either drug from propionic acid by an entirely different mechanism. It enhances the flux of propionic acid into the skin, thus promoting the partitioning of the purine solute in the modified skin barrier ("pull" effect). Indeed, the magnitude of vi of either purine in propionic acid:paraffin oil solution gives no indication of a significant interaction between paraffin oil and the purine solute. Finally, the penetration enhancing effects of PEG-2-L and paraffin oil combined together in the same propionic acid vehicle are additive, resulting in a flux which is approximately the sum total of fluxes obtained separately with PEG-2-L or paraffin oil.

Nano-particle dynamics during capillary suction.

PubMed

Kuijpers, C J; Huinink, H P; Tomozeiu, N; Erich, S J F; Adan, O C G

2018-07-01

Due to the increased use of nanoparticles in everyday applications, there is a need for theoretical descriptions of particle transport and attachment in porous media. It should be possible to develop a one dimensional model to describe nanoparticle retention during capillary transport of liquid mixtures in porous media. Water-glycerol-nanoparticle mixtures were prepared and the penetration process in porous Al 2 O 3 samples of varying pore size is measured using NMR imaging. The liquid and particle front can be measured by utilizing T 2 relaxation effects from the paramagnetic nanoparticles. A good agreement between experimental data and the predicted particle retention by the developed theory is found. Using the model, the binding constant for Fe 2 O 3 nanoparticles on sintered Al 2 O 3 samples and the maximum surface coverage are determined. Furthermore, we show that the penetrating liquid front follows a square root of time behavior as predicted by Darcy's law. However, scaling with the liquid parameters is no longer sufficient to map different liquid mixtures onto a single master curve. The Darcy model should be extended to address the two formed domains (with and without particles) and their interaction, to give an accurate prediction for the penetrating liquid front. Copyright © 2018 Elsevier Inc. All rights reserved.

Loss of surface coat by Strongyloides ratti infective larvae during skin penetration: evidence using larvae radiolabelled with /sup 67/gallium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grove, D.I.; Northern, C.; Warwick, A.

1984-10-01

The optimal conditions for labelling infective larvae of Strongyloides ratti with /sup 67/Ga citrate were determined. Radiolabelled larvae were injected s.c. into normal and previously infected rats. The distribution of radioactivity in these animals was compared with that in rats infected subcutaneously with a similar dose of free /sup 67/Ga by using a gamma camera linked to a computer system. Whereas free /sup 67/Ga was distributed throughout the body and excreted via the hepatobiliary system, the bulk of radioactivity in rats injected with radiolabelled larvae remained at the injection sites. Direct microscopical examination of these sites, however, revealed only minimalmore » numbers of worms. When rats were infected percutaneously with radiolabelled larvae, it was found that most radioactivity remained at the surface, despite penetration of worms. When infective larvae were exposed to CO/sub 2/ in vitro and examined carefully by light microscopy, loss of an outer coat was observed. It was concluded that infective larvae lose an outer coat on skin penetration.« less

Effect of natural extracts pH on morphological characteristics of hybrid materials based on gold nanoparticles

NASA Astrophysics Data System (ADS)

Olenic, L.; Vulcu, A.; Chiorean, I.; Crisan, M.; Berghian-Grosan, C.; Dreve, S.; David, L.; Tudoran, L. B.; Kacso, I.; Bratu, I.; Neamtu, C.; Voica, C.

2013-11-01

In the present paper we have investigated the pH influence on the morphology of some new hybrid materials based on gold nanoparticles and natural extracts from fruits of Romanian native plants of Adoxaceae family (Viburnum opulus L. and Sambucus nigra L.). It is well known that the natural plants extracts are beneficial for humans thanks to their antioxidant, anti-inflammatory and immunomodulatory effects. The biological activity of these berries is mainly due to their high content of anthocyanins and other polyphenols. The nanoparticles facilitate the penetration of substances in skin, enhancing their antimitotic, anti-inflammatory and antibiotic properties. We have chosen the optimal method to get these materials in which gold nanoparticles of 10-80 nm were obtained. We characterized them by UV-Vis and FT-IR spectroscopy, by TEM and DSC. Creams prepared with the hybrid materials have been tested on psoriatic lesions and the medical results emphasized a remarkable improvement in this diseases.

Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil: in vitro evaluation of drug permeation by infrared spectroscopy.

PubMed

Mura, Simona; Manconi, Maria; Fadda, Anna Maria; Sala, Maria Chiara; Perricci, Jacopo; Pini, Elena; Sinico, Chiara

2013-01-01

Recently, we carried out a research on new liposomal systems prepared by using in their composition a few penetration enhancers which differ for chemical structure and physicochemical properties. The penetration enhancer-containing vesicles (PEVs) were prepared by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy) ethanol (Transcutol(®)), capryl-caproyl macrogol 8-glyceride (Labrasol(®)), and cineole.To study the influence of the PEVs on (trans)dermal delivery of minoxidil, in vitro diffusion experiments were performed through new born pig skin and the results were compared with that obtained applying the vesicular system without enhancer (control) after pretreatment of the skin with the various enhancers. In this study, Fourier transform infrared spectroscopy (FTIR), attenuated total reflectance FTIR (ATR-FTIR) and FTIR imaging were used to evaluate the effective penetration of minoxidil in the skin layers and to discover the influence of the enhancer on the drug topical delivery. These analytical studies allowed us to characterize the drug formulations and to evaluate the vesicle distribution into the skin. Recorded spectra confirmed that the vesicle formulations with penetration enhancers promoted drug deposition into the skin.

Phosphatidylcholine embedded micellar systems: enhanced permeability through rat skin.

PubMed

Spernath, Aviram; Aserin, Abraham; Sintov, Amnon C; Garti, Nissim

2008-02-15

Micellar and microemulsion systems are excellent potential vehicles for delivery of drugs because of their high solubilization capacity and improved transmembrane bioavailability. Mixtures of propylene glycol (PG) and nonionic surfactants with sodium diclofenac (DFC) were prepared in the presence of phosphatidylcholine (PC) as transmembrane transport enhancers. Fully dilutable systems with maximum DFC solubilization capacity (SC) at pH 7 are presented. It was demonstrated that the concentrates underwent phase transitions from reverse micelles to swollen reverse micelles and, via the bicontinuous transitional mesophase, into inverted O/W microstructures. The SC decreases as a function of dilution. DFC transdermal penetration using rat skin in vitro correlated with SC, water content, effect of phospholipid content, presence of an oil phase, and ethanol. Skin penetration from the inverted bicontinuous mesophase and the skin penetration from the O/W-like microstructure were higher than that measured from the W/O-like droplets, especially when the micellar system containing the nonionic surfactant, sugar ester L-1695, and hexaglycerol laurate. PC embedded within the micelle interface significantly increased the penetration flux across the skin compared to micellar systems without the embedded PC at their interface. Moreover, the combination of PC with HECO40 improved the permeation rate (P) and shortened the lag-time (T(L)).

Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.

PubMed

Jain, Arvind K; Massey, Ashley; Yusuf, Helmy; McDonald, Denise M; McCarthy, Helen O; Kett, Vicky L

2015-01-01

We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

Development of polymeric–cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery

PubMed Central

Jain, Arvind K; Massey, Ashley; Yusuf, Helmy; McDonald, Denise M; McCarthy, Helen O; Kett, Vicky L

2015-01-01

We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid–polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA. PMID:26648722

Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With an Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability.

PubMed

Sallam, Marwa Ahmed; Marín Boscá, María Teresa

2017-10-01

This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-ε-caprolactone nanospheres (NS) with an encapsulation efficiency of 84.73% ± 1.52%, a particle size of 107.5 ± 8.19 nm, and zeta potential of -13.1 mV demonstrating a sustained-release behavior. The AD-NS were embedded in either hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gel. The ex vivo human skin dermatokinetics of AD from each system was studied. The nanoparticles dispersion showed significantly higher AD retention in the epidermis and dermis than AD suspension. NS-HPMC decreased whereas NS-HA increased AD retained in all the skin layers. The fate of the NS and the role of the hydrogel in modulating skin distribution was evaluated by confocal laser scanning microscopy (CLSM) imaging of fluorescently labeled NS. CLSM illustrated follicular localization of the florescent NS. HPMC gel restricted the presence of NS to the stratum corneum and epidermis. HA gel enhanced the penetration of NS to all the skin layers. In vitro skin irritation using human dermal fibroblasts and in vivo animal tolerability studies were performed. Accordingly, HA gel-dispersed AD-NS presented a nonirritant compromised cosmeceutical formulation suitable for oily acneic skin. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Dependence of light transmission through human skin on incident beam diameter at different wavelengths

NASA Astrophysics Data System (ADS)

Zhao, ZhongQuan; Fairchild, Paul W.

1998-05-01

For many skin treatments with light, it is important to have deep photon penetration into the skin. Because of absorption and scattering of photons by skin tissue, both the color and the diameter of the incident beam affect the penetration depth of photons. In this study, the dependence of light transmission through human skin tissues (ear lobs and between the fingers) has been measured in-vivo at six wavelengths (532 nm, 632 nm, 675 nm, 810 nm, 911 nm, and 1064 nm). The same measurement was also made on pig skin in-vitro for comparison. It was observed that (1) the photons at 1064 nm penetrate deeper than the other colors studied for a given incident beam diameter; and (2) the transmittance at a particular wavelength increases asymptotically with incident beam diameter. For some skin tissues, the transmittance flattens at about 8 mm for 532 nm photons and approaches saturation at about 12 mm for all other colors. The results on pig skin is similar.

Genotoxicity, acute oral and dermal toxicity, eye and dermal irritation and corrosion and skin sensitisation evaluation of silver nanoparticles.

PubMed

Kim, Jin Sik; Song, Kyung Seuk; Sung, Jae Hyuck; Ryu, Hyun Ryol; Choi, Byung Gil; Cho, Hyun Sun; Lee, Jin Kyu; Yu, Il Je

2013-08-01

To clarify the health risks related to silver nanoparticles (Ag-NPs), we evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation, dermal irritation and corrosion and skin sensitisation of commercially manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs were not found to induce genotoxicity in a bacterial reverse mutation test and chromosomal aberration test, although some cytotoxicity was observed. In acute oral and dermal toxicity tests using rats, none of the rats showed any abnormal signs or mortality at a dose level of ∼ 2000 mg/kg. Similarly, acute eye and dermal irritation and corrosion tests using rabbits revealed no significant clinical signs or mortality and no acute irritation or corrosion reaction for the eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20) showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin sensitiser.

Color structured light imaging of skin

NASA Astrophysics Data System (ADS)

Yang, Bin; Lesicko, John; Moy, Austin; Reichenberg, Jason; Sacks, Michael; Tunnell, James W.

2016-05-01

We illustrate wide-field imaging of skin using a structured light (SL) approach that highlights the contrast from superficial tissue scattering. Setting the spatial frequency of the SL in a regime that limits the penetration depth effectively gates the image for photons that originate from the skin surface. Further, rendering the SL images in a color format provides an intuitive format for viewing skin pathologies. We demonstrate this approach in skin pathologies using a custom-built handheld SL imaging system.

Follicular and percutaneous penetration pathways of topically applied minoxidil foam.

PubMed

Blume-Peytavi, Ulrike; Massoudy, Lida; Patzelt, Alexa; Lademann, Jürgen; Dietz, Ekkehart; Rasulev, Utkur; Garcia Bartels, Natalie

2010-11-01

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery. Copyright © 2010 Elsevier B.V. All rights reserved.

Delivery and reveal of localization of upconversion luminescent microparticles and quantum dots in the skin in vivo by fractional laser microablation, multimodal imaging, and optical clearing.

PubMed

Volkova, Elena K; Yanina, Irina Yu; Genina, Elina A; Bashkatov, Alexey N; Konyukhova, Julia G; Popov, Alexey P; Speranskaya, Elena S; Bucharskaya, Alla B; Navolokin, Nikita A; Goryacheva, Irina Yu; Kochubey, Vyacheslav I; Sukhorukov, Gleb B; Meglinski, Igor V; Tuchin, Valery V

2018-02-01

Delivery and spatial localization of upconversion luminescent microparticles [Y2O3:Yb, Er] (mean size ∼1.6  μm) and quantum dots (QDs) (CuInS2/ZnS nanoparticles coated with polyethylene glycol-based amphiphilic polymer, mean size ∼20  nm) inside rat skin was studied in vivo using a multimodal optical imaging approach. The particles were embedded into the skin dermis to the depth from 300 to 500  μm through microchannels performed by fractional laser microablation. Low-frequency ultrasound was applied to enhance penetration of the particles into the skin. Visualization of the particles was revealed using a combination of luminescent spectroscopy, optical coherence tomography, confocal microscopy, and histochemical analysis. Optical clearing was used to enhance the image contrast of the luminescent signal from the particles. It was demonstrated that the penetration depth of particles depends on their size, resulting in a different detection time interval (days) of the luminescent signal from microparticles and QDs inside the rat skin in vivo. We show that luminescent signal from the upconversion microparticles and QDs was detected after the particle delivery into the rat skin in vivo during eighth and fourth days, respectively. We hypothesize that the upconversion microparticles have created a long-time depot localized in the laser-created channels, as the QDs spread over the surrounding tissues. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption.

PubMed

Pfannes, Eva K B; Weiss, Lina; Hadam, Sabrina; Gonnet, Jessica; Combardière, Béhazine; Blume-Peytavi, Ulrike; Vogt, Annika

2018-01-01

The success of topically applied treatments on skin relies on the efficacy of skin penetration. In order to increase particle or product penetration, mild skin barrier disruption methods can be used. We previously described cyanoacrylate skin surface stripping as an efficient method to open hair follicles, enhance particle penetration, and activate Langerhans cells. We conducted ex vivo and in vivo measurements on human skin to characterize the biological effect and quantify barrier disruption-related inflammation on a molecular level. Despite the known immunostimulatory effects, this barrier disruption and hair follicle opening method was well accepted and did not result in lasting changes of skin physiological parameters, cytokine production, or clinical side effects. Only in ex vivo human skin did we find a discrete increase in IP-10, TGF-β, IL-8, and GM-CSF mRNA. The data underline the safety profile of this method and demonstrate that the procedure per se does not cause substantial inflammation or skin damage, which is also of interest when applied to non-invasive sampling of biomarkers in clinical trials. © 2018 S. Karger AG, Basel.

Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.

PubMed

Pati, Rashmirekha; Mehta, Ranjit Kumar; Mohanty, Soumitra; Padhi, Avinash; Sengupta, Mitali; Vaseeharan, Baskarlingam; Goswami, Chandan; Sonawane, Avinash

2014-08-01

Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis-BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis-GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus. Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections. This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications. Copyright © 2014 Elsevier Inc. All rights reserved.

Application of water-soluble polyvinyl alcohol-based film patches on laser microporated skin facilitates intradermal macromolecule and nanoparticle delivery.

PubMed

Engelke, Laura; Winter, Gerhard; Engert, Julia

2018-07-01

The intradermal delivery of biologics has long been recognized as attractive approach for cutaneous immunotherapy, particularly vaccination. Although intradermal (i.d.) or subcutaneous (s.c.) injection provide reproducible dosing and good cost- and delivery efficiency, the major objective to avoid sharps and the need for enhanced storage stability have renewed the interest in alternative needle-free delivery strategies. This study presents a new concept for the delivery of macromolecules and nanoparticles to viable skin layers with a high density of professional antigen-presenting cells (APCs). Stable polyvinyl alcohol (PVA) polymer films as well as PVA blends with carboxymethyl cellulose (CMC) or cross-linked carbomer were prepared using an easily-scalable film casting technique. Fluorescein isothiocyanate (FITC) and rhodamine B-labeled dextrane 70 kDa (RD70), used as small and macromolecular model substances, or polystyrene (PS)-nano- and microparticles with diameters of 0.5 µm and 5 µm were directly incorporated into the polymer formulations at varying concentrations. The assembly of the polymer films with an occlusive backing tape created a film patch that provided a fast drug release upon dissolution of the water-soluble film and facilitated an intradermal drug delivery on laser microporated skin. The minimally-invasive P.L.E.A.S.E.® laser poration system (Pantec Biosolutions, Ruggell, Liechtenstein) provided access to viable skin layers by thermally ablating the superficial tissue with a pulsed Er:YAG laser (λ = 2.94 µm). In our in vitro study using excised pig skin, laser microporation induced a 4- to 5-fold increase of water transport (TEWL) through excised skin in a Franz diffusion cell compared to intact skin. The TEWL values detected were comparable to in vivo human skin. The increased water transport facilitated the dissolution of all topically applied dry PVA-based film formulations within 6 h. No dissolution of the films was seen on

Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: further delineation of the skin phenotype in a prospective epidemiological study of 792 school children

PubMed Central

Brown, SJ; Relton, CL; Liao, H; Zhao, Y; Sandilands, A; McLean, WHI; Cordell, HJ; Reynolds, NJ

2009-01-01

Background Null mutations within the filaggrin gene (FLG) cause ichthyosis vulgaris and are associated with atopic eczema. However, the dermatological features of filaggrin haploinsufficiency have not been clearly defined. Objectives This study investigated the genotype–phenotype association between detailed skin phenotype and FLG genotype data in a population-based cohort of children. Methods Children (n= 792) aged 7–9 years were examined by a dermatologist. Features of ichthyosis vulgaris, atopic eczema and xerosis were recorded and eczema severity graded using the Three Item Severity score. Each child was genotyped for the six most prevalent FLG null mutations (R501X, 2282del4, R2447X, S3247X, 3702delG, 3673delC). Fisher’s exact test was used to compare genotype frequencies in phenotype groups; logistic regression analysis was used to estimate odds ratios and penetrance of the FLG null genotype and a permutation test performed to investigate eczema severity in different genotype groups. Results Ten children in this cohort had ichthyosis vulgaris, of whom five had mild–moderate eczema. The penetrance of FLG null mutations with respect to flexural eczema was 55·6% in individuals with two mutations, 16·3% in individuals with one mutation and 14·2% in wild-type individuals. Summating skin features known to be associated with FLG null mutations (ichthyosis, keratosis pilaris, palmar hyperlinearity and flexural eczema) showed a penetrance of 100% in children with two FLG mutations, 87·8% in children with one FLG mutation and 46·5% in wild-type individuals (P< 0·0001, Fisher exact test). FLG null mutations were associated with more severe eczema (P= 0·0042) but the mean difference was only 1–2 points in severity score. Three distinct patterns of palmar hyperlinearity were observed and these are reported for the first time. Conclusions Filaggrin haploinsufficiency appears to be highly penetrant when all relevant skin features are included in the

Dermal in vitro penetration of methiocarb, paclobutrazol, and pirimicarb: effect of nonylphenolethoxylate and protective gloves.

PubMed Central

Nielsen, J B; Andersen, H R

2001-01-01

Dermal exposure has become the major route of human occupational exposure to pesticides. Detergents are used as part of formulated pesticide products and are known to change the barrier properties of human skin in vitro. However, studies on the influence of detergents as well as protective glove materials on dermal penetration of pesticides are scarce. In an experiment using in vitro static diffusion cells mounted with human skin, we evaluated the effect of nonylphenol-ethoxylate on dermal penetration of three extensively used pesticides--methiocarb, paclobutrazol, and pirimicarb--and the protection against dermal penetration offered by protective gloves made of latex or nitrile. There was a general tendency, though not statistically significant for all pesticides, for nonylphenolethoxylate to decrease the percutaneous penetration of the three pesticides. The nitrile generally offered better protection against percutaneous penetration of pesticides than did latex, but the degree of protection decreased over time and depended on the pesticides used. PMID:11266321

Cutaneous estradiol permeation, penetration and metabolism in pig and man.

PubMed

Mahmoud, A; Haberland, A; Dürrfeld, M; Heydeck, D; Wagner, S; Schafer-Korting, M

2005-01-01

Drug development in dermatotherapy and also development of transdermal therapeutic systems (TTS) demand high-predictive in vitro models to estimate drug levels in skin and systemic uptake. Here we compare three ready-to-use models, reconstructed human epidermis, split porcine skin and the perfused porcine forelimb. 17beta-Estradiol (E(2)), which is highly metabolized by skin cells, serves as model drug since E(2) application is of high relevance in hormone replacement therapy while topical E(2) may promote wound healing. E(2) TTS, gel and an ethanolic solution were investigated for cutaneous penetration, permeation and metabolism. E(2) TTS enabled an E(2) uptake of 42.9% of the applied dose accompanied by a high percentage of E(2) metabolism (30% of the penetrated dose) in the perfused porcine forelimb. In Franz cell experiments with reconstructed human epidermis and split porcine skin, the gel allowed an E(2) uptake of 41.7 and 22.9% of the applied dose accompanied by a high E(2) metabolism (42.6 and 28.6% of the penetrated dose). Due to toxic effects of the vehicle, this was not true with an ethanolic solution, then E(2) permeation and metabolism were clearly diminished. Most importantly, the in vitro models proved to be predictive with respect to the E(2)/estrone ratio in female plasma under transdermal hormone replacement therapy. In vitro tests should reduce the need for both animal and human studies for cutaneous uptake and metabolism in the future. Copyright 2005 S. Karger AG, Basel.

Skin penetration of silicon dioxide microneedle arrays.

PubMed

Kim, Sangchae; Shetty, S; Price, D; Bhansali, S

2006-01-01

Out-of-plane hollow silicon dioxide microneedle arrays were fabricated and investigated to determine their efficacy for transdermal applications. The fabrication process of the SiO2 microneedles is described, and mechanical fracture forces were investigated on microneedles with different geometrical dimensions. Biomechanical characterization of the microneedles was performed to specifically test for reliable stratum corneum and skin insertion by changing the regulatory parameters such as needle width and cross-section.

Allergic Responses Induced by the Immunomodulatory Effects of Nanomaterials upon Skin Exposure

PubMed Central

Yoshioka, Yasuo; Kuroda, Etsushi; Hirai, Toshiro; Tsutsumi, Yasuo; Ishii, Ken J.

2017-01-01

Over the past decade, a vast array of nanomaterials has been created through the development of nanotechnology. With the increasing application of these nanomaterials in various fields, such as foods, cosmetics, and medicines, there has been concern about their safety, that is, nanotoxicity. Therefore, there is an urgent need to collect information about the biological effects of nanomaterials so that we can exploit their potential benefits and design safer nanomaterials, while avoiding nanotoxicity as a result of inhalation or skin exposure. In particular, the immunomodulating effect of nanomaterials is one of most interesting aspects of nanotoxicity. However, the immunomodulating effects of nanomaterials through skin exposure have not been adequately discussed compared with the effects of inhalation exposure, because skin penetration by nanomaterials is thought to be extremely low under normal conditions. On the other hand, the immunomodulatory effects of nanomaterials via skin may cause severe problems for people with impaired skin barrier function, because some nanomaterials could penetrate the deep layers of their allergic or damaged skin. In addition, some studies, including ours, have shown that nanomaterials could exhibit significant immunomodulating effects even if they do not penetrate the skin. In this review, we summarize our current knowledge of the allergic responses induced by nanomaterials upon skin exposure. First, we discuss nanomaterial penetration of the intact or impaired skin barrier. Next, we describe the immunomodulating effects of nanomaterials, focusing on the sensitization potential of nanomaterials and the effects of co-exposure of nanomaterials with substances such as chemical sensitizers or allergens, on the onset of allergy, following skin exposure. Finally, we discuss the potential mechanisms underlying the immunomodulating effects of nanomaterials by describing the involvement of the protein corona in the interaction of

Studying the effectiveness of penetration enhancers to deliver retinol through the stratum cornum by in vivo confocal Raman spectroscopy.

PubMed

Mélot, Mickaël; Pudney, Paul D A; Williamson, Ann-Marie; Caspers, Peter J; Van Der Pol, Andre; Puppels, Gerwin J

2009-08-19

The purpose of this study is to monitor in vivo the effect of chemical penetration enhancers on the delivery of trans-retinol into human skin. Chemical penetration enhancers reversibly alter barrier properties of the SC by disruption of the membrane structures or maximising drug solubility with the skin. So far, most of permeation or penetration experiments are performed in vitro. Raman spectroscopy is uniquely placed to be able to measure biological processes in vivo and this paper shows for the first time that the effect of penetration enhancer on the delivery of trans-retinol can successfully be measured in vivo using this technique. Here, the volar forearm of volunteers was treated with four formulations. One formulation is a highly effective model delivery system identified from ex vivo experiments: trans-retinol in Propylene Glycol (PG)/ethanol, with PG being a well-known and efficient penetration enhancer. The other three formulations are based on 0.3% trans-retinol in Caprylic/Capric Acid Triglyceride (MYRITOL 318), an oil commonly used in skin creams but in two of them a specific penetration enhancer is added. One contains a lipid extractor, Triton X 100, whereas another formulation contains a lipid fluidiser, Oleic Acid. Solutions were applied once and measurements were performed up to 6 h after treatment. Remarkable differences in the delivery of trans-retinol between formulation with or without penetration enhancer can clearly be seen. Moreover, the type of penetration enhancer is also shown to influence the delivery. While using the Oleic Acid, which is a lipid fluidiser, a better delivery of trans-retinol in the skin can be detected. For the first time, the effect of penetration enhancer on the delivery of trans-retinol has been monitored, non invasively in vivo, with time.

Polyamide nanocapsules and nano-emulsions containing Parsol® MCX and Parsol® 1789: in vitro release, ex vivo skin penetration and photo-stability studies.

PubMed

Hanno, Ibrahim; Anselmi, Cecilia; Bouchemal, Kawthar

2012-02-01

To prepare polyamide nanocapsules for skin photo-protection, encapsulating α-tocopherol, Parsol®MCX (ethylhexyl methoxycinnamate) and/or Parsol®1789 (butyl methoxydibenzoylmethane). Nanocapsules were obtained by combining spontaneous emulsification and interfacial polycondensation reaction between sebacoyl chloride and diethylenetriamine. Nano-emulsions used as control were obtained by the same process without monomers. The influence of carrier on release rate was studied in vitro with a membrane-free model. Epidermal penetration of encapsulated sunscreens was ex vivo evaluated using Franz diffusion cells. Ability of encapsulated sunscreens to improve photo-stability was verified by comparing percentage of degradation after UV radiation exposure. Sunscreen-containing nanocapsules (260-400 nm) were successfully prepared; yield of encapsulation was >98%. Parsol®MCX and Parsol®1789 encapsulation led to decreased release rate by up to 60% in comparison with nano-emulsion and allowed minimum penetration through pig ear epidermis. Presence of polyamide shell protected encapsulated sunscreen filters from photo-degradation without affecting their activity. Encapsulation of Parsol®MCX and Parsol®1789 into oil-core of polyamide nanocapsules allowed protection from photo-degradation, controlled release from nanocapsules, and limited penetration through pig ear epidermis.

Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles

PubMed Central

Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Verma, Ankit; Ahamed, Maqusood; Ahmed, Mukhtar; Alhadlaq, Hisham A

2013-01-01

The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles. PMID:23493450