dermal penetration
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2022 ◽  
Author(s):  
Nikhat J. Siddiqi ◽  
Sabiha Fatima ◽  
Bechan Sharma ◽  
Mohamed Samir Elrobh

The unique physicochemical properties of nanoparticles (NPs) make them widely used in cosmetics, medicines, food additives, and antibacterial and antiviral compounds. NPs are also used in therapy and diagnostic applications. Depending on their origin, the NPs are commonly classified as naturally occurring and synthetic or anthropogenic NPs. Naturally occurring nanoparticles can be formed by many physical, chemical, and biological processes occurring in all spheres of the earth. However, synthetic NPs are specifically designed or unintentionally produced by different human activities. Owing to their nano size and special properties, the engineered NPs can enter the human body through different routes such as dermal penetration, intravenous injection and inhalation. NPs may accumulate in various tissues and organs including the brain. Indiscriminate use of NP is a matter concern due to the dangers of NP exposure to living organisms. It is possible for NPs to cross the placental barrier, and adversely affect the developing fetus, posing a health hazard in them by causing neurodevelopmental toxicity. Thus, NP-induced neurotoxicity is a topic that demands attention at the maternal-fetal interface. This chapter summarizes the routes by which NPs circumvent the blood-brain barrier, including recent investigations about NPs’ neurotoxicity as well as possible mechanisms involved in neural fetotoxicity.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2190
Author(s):  
Vasudha Kaushik ◽  
Yameera Ganashalingam ◽  
Robert Schesny ◽  
Christian Raab ◽  
Soma Sengupta ◽  
...  

The study aimed at comparing the influence of direct and indirect skin hydration as well as massage on the dermal penetration efficacy of active compounds. Nile red was used as a lipophilic drug surrogate and was incorporated into Vaseline (petroleum jelly). The formulation was applied with and without massage onto either dry skin or pre-hydrated, moist skin. It was expected that the occlusive properties of Vaseline in combination with massage and enhanced skin hydration would cause a superposition of penetration-enhancing effects, which should lead to a tremendous increase in the dermal penetration efficacy of the lipophilic drug surrogate. Results obtained were diametral to the expectations, and various reasons were identified for causing the effect observed. Firstly, it was found that Vaseline undergoes syneresis after topical application. The expulsed mineral oil forms a film on top of the skin, and parts of it penetrate into the skin. The lipophilic drug surrogate, which is dissolved in the mineral oil, enters the skin with the mineral oil, i.e., via a solvent drag mechanism. Secondly, it was found that massage squeezes the skin and causes the expulsion of water from deeper layers of the SC. The expulsed water can act as a water barrier that prevents the penetration of lipophilic compounds and promotes the penetration of hydrophilic compounds. Based on the data, it is concluded that dermal penetration is a complex process that cannot only be explained by Fick’s law. It is composed of at least three different mechanisms. The first mechanism is the penetration of active ingredients with their solvents into the skin (convection, solvent drag), the second mechanism is the penetration of the active ingredient via passive diffusion, and the third mechanism can involve local penetration phenomena, e.g., the formation of liquid menisci and particle-associated penetration enhancement, which occur upon the evaporation of water and/or other ingredients from the formulation on top of the skin.


Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2387
Author(s):  
Anna Lena Klein ◽  
Markus Lubda ◽  
David Specht ◽  
Sung-Min Pyo ◽  
Loris Busch ◽  
...  

Common ex vivo methods for penetration investigations often fail to monitor transfollicular penetration appropriately. In the present investigation, the validity of dermal microdialysis on the ex vivo porcine ear skin to investigate penetration kinetics, including transfollicular penetration, was studied. In setup A, a caffeine nanocrystal formulation was compared to a non-particular caffeine gel formulation. In setup B, two caffeine nanocrystal formulations of different sizes (200 nm, 700 nm) were compared to each other. Microdialysis samples were collected for 46 h. After sampling, the skin layers were separated, homogenized, and caffeine was quantified in all samples. In setup A the area under the curve (AUC) after crystal gel formulation application was 12 times higher than after non-particular formulation application. Setup B showed an increased AUC of 42% in the microdialysis data when the 700 nm caffeine crystals were applied compared to the 200 nm crystals. The microdialysis data was supported by the separation, homogenization and extraction data. Microdialysis performed on ex vivo porcine ear skin is a novel experimental setup. It is of high interest for further investigations since it is able to also capture the impact of follicular and transfollicular penetration kinetics as no other ex vivo setup can.


Author(s):  
Sabrina Wiemann ◽  
Cornelia M. Keck

AbstractLipid nanoparticles are a successful carrier system for dermal drug delivery. They possess various beneficial properties, i.e., increased chemical stability for chemically labile compounds, increased dermal penetration of active compounds, or skin carrying properties after dermal application due to the formation of a so-called “invisible patch.” Despite manifold studies showing these properties individually, a study that investigates if one lipid nanoparticle formulation can really combine all the above-mentioned benefits at once is not yet available. In the present study, lipid nanoparticles (NLC) were produced and characterized regarding their physico-chemical properties. The chemical stability of the incorporated active ingredient (AI) was determined, as well as the dermal penetration efficacy of the AI, and the skin carrying properties of the NLC after dermal penetration. The properties of the NLC were compared to classical formulations, i.e., AI dissolved in pure oil, an o/w cream base and a nanoemulsion. All formulations contained similar lipids and emulsifiers, which allowed for a direct comparison of the different properties. NLC were shown to provide most efficient chemical stabilization and most efficient dermal penetration for the AI. The formation of the invisible patch was shown for the NLC but not for the other formulations. Skin hydration and skin carrying properties were also most pronounced for the NLC. Results provide evidence that NLC can combine all beneficial effects that were previously described in one formulation. Thus, providing evidence that NLC are a holistically superior formulation principle when compared to other formulation principles. Graphical abstract


2021 ◽  
pp. 1-19
Author(s):  
Olga Pelikh ◽  
Shashank R. Pinnapireddy ◽  
Cornelia M. Keck

<b><i>Introduction:</i></b> Curcumin is a promising drug candidate, but its use for dermal application is limited due to its poor aqueous solubility. Thus, formulations that increase the solubility of curcumin are needed to fully exploit the therapeutic potential of curcumin. Various previous studies address this issue, but a comparison of the efficacy between these formulations remains difficult. The reason for this is a missing standard formulation as benchmark control and an easy-to-use skin penetration model that allows for a fast discrimination between different formulations. <b><i>Objective:</i></b> Thus, the aims of this study were the development of a curcumin standard formulation and a screening tool that allows for a fast discrimination between the dermal penetration efficacies of curcumin from different formulations. <b><i>Methods:</i></b> Ethanolic curcumin solutions were selected as simple and easy to produce standard formulations, and the ex vivo porcine ear model, coupled with epifluorescence microscopy and subsequent digital image analysis, was utilized to determine the dermal penetration efficacy of curcumin from the different formulations. <b><i>Results:</i></b> Results show that the utilized skin penetration model is a suitable and versatile tool that enables not only a fast determination of the dermal penetration efficacy of curcumin from different formulations but also a detailed and mechanistic information on the fate of chemical compounds after dermal penetration. Ethanolic solutions containing 0.25% curcumin were found to be the most suitable standard formulation. <b><i>Conclusions:</i></b> Results of the study provide a new, effective screening tool for the development of dermal formulations for improved dermal delivery of curcumin.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1633
Author(s):  
Ralph W. Eckert ◽  
Sabrina Wiemann ◽  
Cornelia M. Keck

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 320
Author(s):  
Anna Otterbach ◽  
Alf Lamprecht

Dimethyl sulfoxide is a well-known and widely used dermal penetration enhancer. Its incorporation in transdermal patches would be highly desirable; however, due to its volatility this is extremely challenging. Here, we report on the feasibility of a dimethyl sulfoxide (DMSO) containing transdermal system containing estradiol as a model compound. Transdermal patches were prepared from duro-tak® 387-2510 containing various DMSO concentrations at different drying temperatures. The resulting patches were analyzed for DMSO content, estradiol and DMSO release, estradiol and DMSO permeation through excised porcine skin, and recrystallization during stability testing. Drying conditions in the range of 35° to 40° allowed a complete polymer solvents removal while retaining significant amounts of DMSO (≤10 mg/patch). Estradiol skin permeation increased 4-fold (Jss = 4.12 µg/cm−2·h−1) compared to DMSO-negative control (Jss = 1.1 ± 0.2 µg/cm−2·h−1). As additional benefit, estradiol recrystallization was inhibited by DMSO at even lowest solvent concentrations. Storage stability was limited to 6 months at 25 °C with a surprising discrepancy between DMSO content (significantly lower) and flux (not significantly different). Although the technical feasibility range is relatively narrow, such DMSO-containing matrix-type patches are able to significantly enhance drug permeation through the skin while ameliorating the product stability against recrystallization.


2021 ◽  
Vol 119 ◽  
pp. 104836
Author(s):  
Irene Gimeno-Benito ◽  
Anna Giusti ◽  
Susan Dekkers ◽  
Andrea Haase ◽  
Gemma Janer

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2323
Author(s):  
Olga Pelikh ◽  
Cornelia M. Keck

Many active pharmaceutical ingredients (API) possess poor aqueous solubility and thus lead to poor bioavailability upon oral administration and topical application. Nanocrystals have a well-established, universal formulation approach to overcome poor solubility. Various nanocrystal-based products have entered the market for oral application. However, their use in dermal formulations is relatively novel. Previous studies confirmed that nanocrystals are a superior formulation principle to improve the dermal penetration of poorly soluble API. Other studies showed that nanocrystals can also be used to target the hair follicles where they create a drug depot, enabling long acting drug therapy with only one application. Very recent studies show that also the vehicle in which the nanocrystals are incorporated can have a tremendous influence on the pathway of the API and the nanocrystals. In order to elucidate the influence of the excipient in more detail, a systematic study was conducted to investigate the influence of excipients on the penetration efficacy of the formulated API and the pathway of nanocrystals upon dermal application. Results showed that already small quantities of excipients can strongly affect the passive dermal penetration of curcumin and the hair follicle targeting of curcumin nanocrystals. The addition of 2% ethanol promoted hair follicle targeting of nanocrystals and hampered passive diffusion into the stratum corneum of the API, whereas the addition of glycerol hampered hair follicle targeting and promoted passive diffusion. Propylene glycol was found to promote both pathways. In fact, the study proved that formulating nanocrystals to improve the bioefficacy of poorly soluble API upon dermal application is highly effective. However, this is only true, if the correct excipient is selected for the formulation of the vehicle. The study also showed that excipients can be used to allow for a targeted dermal drug delivery, which enables to control if API should be delivered via passive diffusion and/or as drug reservoir by depositing API in the hair follicles.


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