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Biophysical Journal Oct 2022A molecular-level understanding of skin permeation may rationalize and streamline product development, and improve quality and control, of transdermal and topical drug...
A molecular-level understanding of skin permeation may rationalize and streamline product development, and improve quality and control, of transdermal and topical drug delivery systems. It may also facilitate toxicity and safety assessment of cosmetics and skin care products. Here, we present new molecular dynamics simulation approaches that make it possible to efficiently sample the free energy and local diffusion coefficient across the skin's barrier structure to predict skin permeability and the effects of chemical penetration enhancers. In particular, we introduce a new approach to use two-dimensional reaction coordinates in the accelerated weight histogram method, where we combine sampling along spatial coordinates with an alchemical perturbation virtual coordinate. We present predicted properties for 20 permeants, and demonstrate how our approach improves correlation with ex vivo/in vitro skin permeation data. For the compounds included in this study, the obtained log K mean square difference was 0.9 cm h.
Topics: Skin Absorption; Skin; Administration, Cutaneous; Permeability; Molecular Dynamics Simulation
PubMed: 36104960
DOI: 10.1016/j.bpj.2022.09.009 -
Journal of Controlled Release :... Oct 2016This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of... (Review)
Review
This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has - and will continue to have - a profound impact on both clinical outcomes and the development of new products.
Topics: Administration, Cutaneous; Animals; Drug Delivery Systems; Humans; Nanofibers; Nanoparticles; Skin Absorption
PubMed: 26518723
DOI: 10.1016/j.jconrel.2015.10.049 -
The AAPS Journal May 2020A computational model was developed to better understand the impact of elevated skin temperatures on transdermal drug delivery and dermal clearance. A simultaneous heat...
A computational model was developed to better understand the impact of elevated skin temperatures on transdermal drug delivery and dermal clearance. A simultaneous heat and mass transport model with emphasis on transdermal delivery system (TDS) applications was developed to address transient and steady-state temperature effects on dermal absorption. The model was tested using representative data from nicotine TDS applied to human skin either in vitro or in vivo. The approximately 2-fold increase of nicotine absorption with a 10°C increase in skin surface temperature was consistent with a 50-65 kJ/mol activation energy for diffusion in the stratum corneum, with this layer serving as the primary barrier for nicotine absorption. Incorporation of a dermal clearance component into the model revealed efficient removal of nicotine via the dermal capillaries at both normal and elevated temperatures. Two-compartment pharmacokinetic simulations yielded systemic drug concentrations consistent with the human pharmacokinetic data. Both in vitro skin permeation and in vivo pharmacokinetics of nicotine delivered from a marketed TDS under normal and elevated temperatures can be satisfactorily described by a simultaneous heat and mass transfer computational model incorporating realistic skin barrier properties and dermal clearance components.
Topics: Administration, Cutaneous; Administration, Topical; Capillaries; Humans; Metabolic Clearance Rate; Nicotine; Patient-Specific Modeling; Skin Absorption; Skin Temperature; Transdermal Patch
PubMed: 32390069
DOI: 10.1208/s12248-020-00451-2 -
Biomedicine & Pharmacotherapy =... Dec 2018Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin.... (Review)
Review
Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin. It is a spontaneous isotropic mixture of lipophilic and hydrophilic substances stabilized by suitable surfactant and co-surfactant. The easy fabrication, long-term stability, enhanced solubilization, biocompatibility, skin-friendly appearance and affinity for both the hydrophilic and lipophilic drug substances make it superior for skin drug delivery over the other carrier systems. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system which successfully delivers the drug to and across the skin. In the present review work, we compiled various attempts made in last 20 years, utilizing the microemulsion for dermal and transdermal delivery of various drugs. The review emphasizes the potency of microemulsion for topical and transdermal drug delivery and its effect on drug permeability.
Topics: Administration, Cutaneous; Administration, Topical; Animals; Drug Carriers; Drug Delivery Systems; Emulsions; Humans; Microspheres; Skin Absorption
PubMed: 30372850
DOI: 10.1016/j.biopha.2018.10.021 -
Current Drug Delivery 2019This overview on skin delivery considers the evolution of the principles of percutaneous absorption and skin products from ancient times to today. Over the ages, it has... (Review)
Review
This overview on skin delivery considers the evolution of the principles of percutaneous absorption and skin products from ancient times to today. Over the ages, it has been recognised that products may be applied to the skin for either local or systemic effects. As our understanding of the anatomy and physiology of the skin has improved, this has facilitated the development of technologies to effectively and quantitatively deliver solutes across this barrier to specific target sites in the skin and beyond. We focus on these technologies and their role in skin delivery today and in the future.
Topics: Administration, Topical; Animals; Drug Delivery Systems; Humans; Pharmaceutical Preparations; Skin; Skin Absorption; Technology
PubMed: 30714524
DOI: 10.2174/1567201816666190201143457 -
Journal of Applied Physiology... Aug 2018By combining galvanic skin conductance (GSC), stratum corneum hydration (HYD) and regional surface sweat rate (RSR) measurements at the arm, thigh, back and chest, we...
By combining galvanic skin conductance (GSC), stratum corneum hydration (HYD) and regional surface sweat rate (RSR) measurements at the arm, thigh, back and chest, we closely monitored the passage of sweat from gland to skin surface. Through a varied exercise-rest protocol, sweating was increased slowly and decreased in 16 male and female human participants (25.3 ± 4.7 yr, 174.6 ± 10.1 cm, 71.3 ± 12.0 kg, 53.0 ± 6.8 ml·kg·min). ∆GSC and HYD increased before RSR, indicating pre-secretory sweat gland activity and skin hydration. ∆GSC and HYD typically increased concomitantly during rest in a warm environment (30.1 ± 1.0°C, 30.0 ± 4.7% relative humidity) and only at the arm did ∆GSC increase before an increase in HYD. HYD increased before RSR, before sweat was visible on the skin, but not to full saturation, contradicting earlier hypotheses. Maximal skin hydration did occur, as demonstrated by a plateau in all regions. Post exercise rest resulted in a rapid decrease in HYD and RSR but a delayed decline in ∆GSC. Evidence for reabsorption of surface sweat into the skin following a decline in sweating, as hypothesized in the literature, was not found. This suggests that skin surface sweat, after sweating is decreased, may not diffuse back into the dermis, but is only evaporated. These data, showing distinctly different responses for the three measured variables, provide useful information about the fate of sweat from gland to surface that is relevant across numerous research fields (e.g., thermoregulation, dermatology, ergonomics and material design). NEW & NOTEWORTHY After sweat gland stimulation, sweat travels through the duct, penetrating the epidermis before appearing on the skin surface. We found that only submaximal stratum corneum hydration was required before surface sweating occurred. However, full hydration occurred only once sweat was on the surface. Once sweating reduces, surface sweat evaporation continues, but there is a delayed drying of the skin. This information is relevant across various research fields, including environmental ergonomics, dermatology, thermoregulation, and skin-interface interactions.
Topics: Adult; Body Temperature Regulation; Exercise; Female; Humans; Male; Rest; Skin; Skin Absorption; Skin Physiological Phenomena; Skin Temperature; Sweat; Sweat Glands; Sweating
PubMed: 29745799
DOI: 10.1152/japplphysiol.00872.2017 -
Experimental Dermatology Sep 2022The analytical technology of Raman spectroscopy has an almost 100-year history. During this period, many modifications and developments happened in the method like... (Review)
Review
The analytical technology of Raman spectroscopy has an almost 100-year history. During this period, many modifications and developments happened in the method like discovery of laser, improvements in optical elements and sensitivity of spectrometer and also more advanced light detection systems. Many types of the innovative techniques appeared (e.g. Transmittance Raman spectroscopy, Coherent Raman Scattering microscopy, Surface-Enhanced Raman scattering and Confocal Raman spectroscopy/microscopy). This review article gives a short description about these different Raman techniques and their possible applications. Then, a short statistical part is coming about the appearance of Raman spectroscopy in the scientific literature from the beginnings to these days. The third part of the paper shows the main application options of the technique (especially confocal Raman spectroscopy) in skin research, including skin composition analysis, drug penetration monitoring and analysis, diagnostic utilizations in dermatology and cosmeto-scientific applications. At the end, the possible role of artificial intelligence in Raman data analysis and the regulatory aspect of these techniques in dermatology are briefly summarized. For the future of Raman Spectroscopy, increasing clinical relevance and in vivo applications can be predicted with spreading of non-destructive methods and appearance with the most advanced instruments with rapid analysis time.
Topics: Artificial Intelligence; Microscopy, Confocal; Skin; Skin Absorption; Spectrum Analysis, Raman
PubMed: 35837832
DOI: 10.1111/exd.14645 -
International Journal of Nanomedicine 2018Nanotechnology is an interdisciplinary science that has developed rapidly in recent years. Metallic nanoparticles (NPs) are increasingly utilized in dermatology and... (Review)
Review
Nanotechnology is an interdisciplinary science that has developed rapidly in recent years. Metallic nanoparticles (NPs) are increasingly utilized in dermatology and cosmetology, because of their unique properties. However, skin exposure to NPs raises concerns regarding their transdermal toxicity. The tight junctions of epithelial cells form the skin barrier, which protects the host against external substances. Recent studies have found that NPs can pass through the skin barrier into deeper layers, indicating that skin exposure is a means for NPs to enter the body. The distribution and interaction of NPs with skin cells may cause toxic side effects. In this review, possible penetration pathways and related toxicity mechanisms are discussed. The limitations of current experimental methods on the penetration and toxic effects of metallic NPs are also described. This review contributes to a better understanding of the risks of topically applied metallic NPs and provides a foundation for future studies.
Topics: Animals; Cell Death; Humans; Metal Nanoparticles; Models, Biological; Skin; Skin Absorption
PubMed: 30122919
DOI: 10.2147/IJN.S170745 -
Contact Dermatitis Apr 2013Although p-phenylenediamine (PPD) has been recognized as an extreme sensitizer for many years, the exact mechanism of sensitization has not been elucidated yet.... (Review)
Review
Although p-phenylenediamine (PPD) has been recognized as an extreme sensitizer for many years, the exact mechanism of sensitization has not been elucidated yet. Penetration and the ability to bind to proteins are the first two hurdles that an allergen has to overcome to be able to sensitize. This review is an overview of studies regarding PPD penetration through skin (analogues) and studies on the amino acids that are targeted by PPD. To complete this review, the auto-oxidation and N-acetylation steps involved in PPD metabolism are described. In summary, under normal hair dyeing exposure conditions, <1% of the applied PPD dose penetrates the skin. The majority (>80%) of PPD that penetrates will be converted into the detoxification products monoacetyl-PPD and diacetyl-PPD by the N-acetyltransferase enzymes. The small amount of PPD that does not become N-acetylated is susceptible to auto-oxidation reactions, yielding protein-reactive PPD derivatives. These derivatives may bind to specific amino acids, and some of the formed adducts might be the complexes responsible for sensitization. However, true in vivo evidence is lacking, and further research to unravel the definite mechanism of sensitization is needed.
Topics: Acetylation; Administration, Topical; Animals; Coloring Agents; Dermatitis, Allergic Contact; Hair Dyes; Humans; Phenylenediamines; Skin Absorption
PubMed: 23510340
DOI: 10.1111/cod.12032 -
Expert Opinion on Drug Delivery 2016Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in... (Review)
Review
INTRODUCTION
Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin.
AREAS COVERED
This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed.
EXPERT OPINION
There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration.
Topics: Administration, Cutaneous; Animals; Drug Delivery Systems; Hot Temperature; Humans; Pharmaceutical Preparations; Skin; Skin Absorption
PubMed: 26808472
DOI: 10.1517/17425247.2016.1136286