Clinical Efficacy of Topical Vitamin C on the Appearance of Wrinkles: A Systematic Literature Review.

PURPOSE: A rise in market demand for anti-aging skin care products has resulted in a proliferation of cosmeceuticals, including products that contain vitamin C. Many topicals containing vitamin C claim to reduce the appearance of wrinkles. However, these claims have not been systematically evaluated. METHODS: A systematic review of literature published between January 2015 and September 2022 was performed per PRISMA guidelines. Scopus, Web of Science, and PubMed were queried for records relevant using the following Medical Subject Heading (MeSH) terms: “Topical Vitamin C OR Ascorbic acid”, “Vitamin C efficacy”, “dermatology”, “cosmetology”, and “skin anti-aging”. Variables of interest included: study type, study location, study duration, sample size, patient description, type and ingredients of the topical formulation, outcome measurement, results, and adverse events. RESULTS: After deduplication, consideration of inclusion and exclusion criteria, and title/abstract screening, 5,428 initial records were reduced to 7 articles, including 4 meeting Level IB criteria, one meeting Level IIA criteria, and 2 meeting Level IIB criteria. Methods for assessing clinical improvements included global photodamage score, skin topography assessment, reflectance confocal microscopy (RCM) skin analysis, Dynamical Atlas, and participant self-assessment.  Conclusions: While 4 of the 7 studies met Level IB evidence, further high-quality, prospective, and comparative studies are indicated to better elucidate the role of topical vitamin C in wrinkle reduction. All the studies used vitamin C in combination with other ingredients or therapeutic mechanisms, thereby complicating any specific conclusions regarding the efficacy of vitamin C. Citation: Sanabria B, Berger LE, Mohd H, et al. Clinical efficacy of topical vitamin C on the appearance of wrinkles: a systematic literature review. J Drugs Dermatol. 2023;22(9):898-904. doi:10.36849/JDD.7332.

The Contest of Nanoparticles: Searching for the Most Effective Topical Delivery of Corticosteroids.

Owing to their complicated pathophysiology, the treatment of skin diseases necessitates a complex approach. Conventional treatment using topical corticosteroids often results in low effectiveness and the incidence of local or even systemic side effects. Nanoformulation of potent anti-inflammatory drugs has been selected as an optimal strategy for enhanced topical delivery of corticosteroids. In order to assess the efficiency of various nanoformulations, we formulated hydrocortisone (HC) and hydrocortisone-17-butyrate (HCB) into three different systems: lipid nanocapsules (LNC), polymeric nanoparticles (PNP), and ethosomes (ETZ). The systems were characterized using dynamic light scattering for their particle size and uniformity and the morphology of nanoparticles was observed by transmission electron microscopy. The nanosystems were tested using ex vivo full thickness porcine and human skin for the delivery of HC and HCB. The skin penetration was observed by confocal microscopy of fluorescently labelled nanosystems. ETZ were proposed as the most effective delivery system for both transdermal and dermal drug targeting but were also found to have a profound effect on the skin barrier with limited restoration. LNC and PNP were found to have significant effects in the dermal delivery of the actives with only minimal transdermal penetration, especially in case of HCB administration.

Expert Systems for Predicting the Bioavailability of Sun Filters in Cosmetic Products, Software vs. Expert Formulator: The Benzophenone-3 Case.

There are only a limited number of molecules in a cosmetic formulation, which can passively cross the stratum corneum and be absorbed into the skin layers. However, some actives should never cross the skin in large concentrations due to their potential for side effects, for example, sunscreens. Artificial intelligence is gaining an increasing role as a predictive tool, and in this regard, we selected the Formulating for Efficacy® Software to forecast the changes in bioavailability of selected topical cosmetic compounds. Using the Franz diffusion cell methodology, various oils were selected as those with low release capability, and these were compared to those suggested by the software in Benzophenone-3-containing formulations. The software was able to predict the lipophilic phases, which, if utilized in the emulsion, were stable and sometimes even more pleasant in appearance and consistency than the reference emulsions prepared by the formulator. To date, however, Formulating for Efficacy® Software still has limitations as far as predicting the hydrophilic phase, as well as not being able to choose the emulsifier or the preservative system.

Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?

Managing pediatric tuberculosis (TB) remains a public health problem requiring urgent and long-lasting solutions as TB is one of the top ten causes of ill health and death in children as well as adolescents universally. Minors are particularly susceptible to this severe illness that can be fatal post-infection or even serve as reservoirs for future disease outbreaks. However, pediatric TB is the least prioritized in most health programs and optimal infection/disease control has been quite neglected for this specialized patient category, as most scientific and clinical research efforts focus on developing novel management strategies for adults. Moreover, the ongoing coronavirus pandemic has meaningfully hindered the gains and progress achieved with TB prophylaxis, therapy, diagnosis, and global eradication goals for all affected persons of varying age bands. Thus, the opening of novel research activities and opportunities that can provide more insight and create new knowledge specifically geared towards managing TB disease in this specialized group will significantly improve their well-being and longevity.

Anti-Melanogenic Mechanism of Tetrahydrocurcumin and Enhancing Its Topical Delivery Efficacy Using a Lecithin-Based Nanoemulsion.

Tetrahydrocurcumin (THC) has been well known for its superior antioxidant properties. Therefore, it is speculated that it might be effective to relieve oxidative stress-induced diseases, such as skin hyperpigmentation. In this work, an in vitro B16F10 melanoma cell model was used to study the impact of THC on the melanogenic process under stressed conditions. It was demonstrated that THC could effectively inhibit the α-MSH (melanocyte-stimulating hormone) induced melanin production in B16F10 melanoma cells and the expressions of three key enzymes involved with the biosynthetic process of melanin, tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), were all significantly reduced. In addition, an in vitro human keratinocyte cell model was used to investigate the potential protective role of THC on H2O2-induced cytotoxicity. It was found that THC could prevent H2O2-induced oxidative stress based on the results of both the cell viability study and the intracellular ROS (reactive oxygen species) study assessed by the flow cytometry. Last, THC was formulated into a lecithin based nanoemulsion, and an in vitro Franz diffusion cell study using Strat-M® membrane concluded that the nanoemulsion could significantly enhance the membrane permeation compared to the unformatted THC suspension. This research demonstrated the anti-melanogenic benefits of THC on the melanoma and keratinocyte cell models and the topical delivery efficacy could be significantly enhanced using a lecithin based nanoemulsion.

Deodorants and antiperspirants: identification of new strategies and perspectives to prevent and control malodor and sweat of the body.

Excessive sweating and body odors in many cultures can cause negative perceptions of an individual and in many cases is related to poor hygiene. Personal hygiene products have been developed with the intention of preventing these undesirable issues. The aim of this paper is to review the main active ingredients used in marketed deodorant and antiperspirant formulations as well as to identify new strategies and future methods to optimize such products and prevent malodor. PubMed and ScienceDirect databases were used to search for studies reporting the use of deodorants and antiperspirants, the compounds used in the formulations, their mechanisms of action and associated controversies, as well as new trends and approaches in the area. Even today, we are still using well-known and established actives such as triclosan and aluminum salts, and these are still the most used compounds in deodorants with bactericidal and antiperspirant properties. These substances have been on the market for more than 40 years, and still there are many questions concerning the safety of both actives. There is a general increased interest globally for lifestyles that focus on sustainability and more natural products such as plant sources and the use of, for example, essential oils. The research that focuses in the area of antiperspirants and deodorants is now more focused on studies of the armpit biochemistry and function and control of the microbiota present in this area. Other possible areas of interest are biotechnological solutions and finding new compounds that will interfere with the biochemistry of the process of sweat decomposition. Further approaches include formulations with probiotics which would maintain the balance of axillary microbiota.

Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation.

The aim of this study was to develop lipid-based nanoparticles that entrapped a high concentration of capsaicin (0.25%) from a capsicum oleoresin extract. The solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were strategically fabricated to entrap capsaicin without a hazardous solvent. Optimized nanosize lipid particles with high capsaicin entrapment and loading capacity were achieved from pair-wise comparison of the solid lipid mixtures consisting of fatty esters and fatty alcohols, representing small and large crystal-structure molecules combined with a compatible liquid lipid and surfactants (crystallinity index = 3%). This report was focused on selectively captured capsaicin from oleoresin in amorphous chili extract-loaded NLCs with 85.27% ± 0.12% entrapment efficiency (EE) and 8.53% ± 0.01% loading capacity (LC). The particle size, polydispersity index, and zeta potential of chili extract-loaded NLCs were 148.50 ± 2.94 nm, 0.12 ± 0.03, and -29.58 ± 1.37 mV, respectively. The favorable zero-order kinetics that prolonged capsaicin release and the significantly faster transdermal penetration of the NLC attributed to the reduction in skin irritation of the concentrated capsaicin NLCs, as illustrated by the in vitro EpiDermTM three-dimensional human skin irritation test and hen's egg test chorioallantoic membrane assay (HET-CAM).

Development and Characterization of a Topical Gel Formulation of Adapalene-TyroSpheres and Assessment of Its Clinical Efficacy.

In this study we aimed to develop a semi-solid formulation of polymeric nanoparticles loaded with adapalene to enhance the efficacy and improve the skin tolerability in acne therapy. An amphiphilic and biocompatible copolymer that self-assembles to nanospheres (known as TyroSpheres) was used to encapsulate adapalene and increase its solubility. A water-soluble viscous agent was applied to prepare a gel formulation of adapalene-loaded TyroSpheres (aapalene-TyroSphere). Particle size, morphology, homogeneity, and rheological characteristics of the adapalene-TyroSphere gel formulations were studied. The formulation with the preferred physical and structural properties was further investigated for in vitro skin irritation and in vivo comedolytic activity in a rhino mouse model. Based on the in vitro skin irritation study encapsulation of adapalene in TyroSphere significantly decreased secretion of pro-inflammatory cytokines (IL-1α and IL-8), confirming that the TyroSphere formulation of adapalene is less irritant than the commercial gel (Differin). TyroSphere gel formulation of adapalene improved the comedolytic properties of the formulation by significantly reducing the size of open utricles in rhino mice compared to Differin treatment. Using TyroSpheres, we were able to develop an alternative topical formulation of adapalene, which is potentially less irritant and more potent than the commercial product.

Isoniazid-loaded orodispersible strips: Methodical design, optimization and in vitro-in silico characterization.

Drug treatment remains the most effective global approach to managing and preventing tuberculosis. This work focuses on formulating and evaluating an optimized polyvinyl alcohol-polyethylene glycol based orodispersible strip containing isoniazid, a first-line anti-tubercular agent. A solvent casting method guided through a Taguchi experimental design was employed in the fabrication, optimization and characterization of the orodispersible strip. The optimized strip was physically amalgamated with a monolayer, uniformly distributed surface geometry. It was 159.2 ±â€¯3.0 µm thick, weighed 36.9 ±â€¯0.3 mg, had an isoniazid load of 99.5 ±â€¯0.8%w/w, disintegration and dissolution times of 17.6 ±â€¯0.9 s and 5.5 ±â€¯0.1 min respectively. In vitro crystallinity, thermal measurements and in silico thermodynamic predictions confirmed the strip's intrinsic miscibility, thermodynamic stability and amorphous nature. A Korsmeyer-Peppas (r = 0.99; n > 1 = 1.07) fitted kinetics typified by an initial burst release of 49.4 ±â€¯1.9% at 4 min and a total of 99.8 ±â€¯3.3% at 30 min was noted. Ex vivo isoniazid permeation through porcine buccal mucosa was bi-phasic and characterized by a 50.4 ±â€¯3.8% surge and 95.6 ±â€¯2.9% at 5 and 120 min respectively. The strip was physicomechanically robust, environmentally stable and non-cytotoxic.

Investigation of microemulsion and microemulsion gel formulations for dermal delivery of clotrimazole.

Dermal delivery of hydrophobic drugs by microemulsion (ME) formulations and effect from ME microstructures were studied. Anti-fungal drug, clotrimazole (CLOT), was used as the model compound. ME formulations possessing different microstructures were prepared using a ME system that contains isopropyl myristate as oil, Labrasol and Cremophor EL as surfactant and co-surfactant, and water. Permeation experiments on human cadaver skin were conducted for ME and the control formulations of different CLOT concentrations. Dermal delivery of CLOT assessed by the dermal tissue drug concentration was found to be significantly higher for MEs when compared with the control formulation, evidenced by dermal retention Enhancement Ratio (ERD) of 5.1, 2.8, and 3.0 for tested O/W, bi-continuous, and W/O MEs, respectively. The highest concentration was observed with O/W ME, suggesting the ME microstructure is an important formulation variable for enhancing dermal delivery efficiency. ME gel formulations prepared by incorporating 1.0%(w/w) of Carbopol980 showed comparable dermal CLOT concentration to MEs, but up to 2.4 fold higher than the commercial CLOT cream product, Lotrimin®. Furthermore, Fluorescein Isothiocynate (FITC), used as a model compound for highly hydrophobic drugs, was also studied for dermal delivery by MEs, and results show consistent ME microstructure effect, suggested by significantly higher FITC concentrations in all skin layers, SC, viable epidermis, and dermis, from O/W ME over bi-continuous and W/O MEs.

‬‬‬‬‬‬‬‬Development and characterization of polymeric nanoparticle-based formulation of adapalene for topical acne therapy‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬.

The purpose of this study is to develop a new formulation of adapalene for the topical treatment of acne. We investigated applicability of polymeric nanocarriers based on tyrosine-derived nanospheres (TyroSpheres) for adapalene delivery. TyroSpheres effectively encapsulated adapalene and substantially enhanced its aqueous solubility, while decreasing the crystallinity of the drug in the formulation. Skin distribution of adapalene via TyroSphere formulation was evaluated ex vivo using human cadaver and porcine ear skin, and this was compared with the commercial adapalene formulation, Differin®. Sustained drug release across stratum corneum in 51 h was observed from TyroSpheres. Additionally, in vitro skin irritation studies demonstrated that encapsulation of adapalene in TyroSpheres significantly reduced the irritancy of the drug to monolayer HaCaTs and reconstituted human epidermis (EpiDerm™, MatTek Corp.). The results suggest that TyroSpheres provide a promising carrier system to deliver hydrophobic drugs to hair follicles and upper epidermis while minimizing skin irritation of the encapsulated drug.

Polymeric nanospheres for topical delivery of vitamin D3.

This study investigates the potential application of polymeric nanospheres (known as TyroSpheres) as a formulation carrier for topical delivery of cholecalciferol (i.e., Vitamin D3, VD3) with the goal to improve the skin delivery and stability of VD3. High drug loading and binding efficiencies were obtained for VD3 when loaded in TyroSpheres. VD3 was released from TyroSpheres in a sustained manner and was delivered across the stratum corneum, which occurred independent of the initial drug loading. An ex vivo skin distribution study showed that TyroSphere formulations delivered 3-10µg of active into the epidermis which was significantly higher than that delivered from Transcutol® (the control vehicle). In addition, an in vitro cytotoxicity assay using keratinocytes confirmed that VD3 encapsulation in the nanoparticles did not alter the drug activity. Photodegradation of VD3 followed zero-order kinetics. TyroSpheres were able to protect the active against hydrolysis and photodegradation, significantly enhancing the stability of VD3 in the topical formulation.

Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing.

The irritancy of topical products has to be investigated to ensure the safety and compliance. Although several reconstructed human epidermal models have been adopted by the Organization for Economic Cooperation and Development (OECD) to replace in vivo animal irritation testing, these models are based on a single cell type and lack dermal components, which may be insufficient to reflect all of the components of irritation. In our study, we investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents (HSEs) for use as irritation screening tool. The acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%) and proliferation for human dermal fibroblasts (HDF) and immortalized human keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were prepared. Increased HDF seeding density up to 5 × 10(4)/cm(2) resulted in APM-HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a differentiation marker, respectively. To assess the use of APM-HSEs for irritation testing, six proficiency chemicals, including three nonirritants (phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The APM-HSEs were able to discriminate nonirritants from irritants based on the viability. Levels of cytokines (interleukin [IL]-1α, IL-1ra, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment groups further assisted the irritancy ranking. In conclusion, we have developed partially differentiated full-thickness APM-HSEs based on acellular porcine peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro irritation screening tool.

Combined Atomistic Molecular Calculations and Experimental Investigations for the Architecture, Screening, Optimization, and Characterization of Pyrazinamide Containing Oral Film Formulations for Tuberculosis Management.

To date, effective treatment, prophylaxis, and control of tuberculosis (TB) infection is mainly dependent on the use of drugs. However, patient noncompliance with prescribed anti-TB treatment schemes remains a major problem confronting successful pharmacotherapeutic outcomes. Thus, the development of alternative delivery systems that can improve adherence for the existing anti-TB bioactives has been intensified in recent times. The aim of this investigation was to engineer an optimal, thermodynamically stable oral film (OF) formulation containing a key anti-TB agent, pyrazinamide (PYZ), employing molecular modeling and experimental tools. Four PYZ-loaded film variants (OF 1, OF 2, OF 3, OF 4) were constructed in silico and then prepared in vitro using the Accelrys Materials Studio software and solvent casting method, respectively. Screening and selection of the optimal OF was based on the computation of the total interaction energy (ET), kinetic energy (EK), solubility parameter (S), and cohesive energy density (CED) as well as determining mass, thickness, dissolution and disintegration times, dissolution pH, drug loading capacity, and surface morphology in vitro. OF 2 was selected as the optimal formulation as it displayed the lowest ET (-8006.28 kcal/mol), dissolution time (9.96 min), disintegration time (56.49 s), and weight (39.33 mg); moderate EK (1052.98 kcal/mol); highest S (44.55 (J/cm(3))(0.5)) and CED (1.99 × 10(9) J/m(3)), slim dimension (166 µm), good and unvarying drug loading capacity (98.04%), acceptable dissolution pH (6.70), and well-layered surface topography. The drug release behavior of the optimal OF 2 was best elucidated with the zero order (R(2) = 0.97) and Korsmeyer-Peppas (R(2) = 0.99) models. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) analyses showed that OF 2 was made of physically mixed multiple component polymeric and nonpolymeric compounds. OF 2 was semicrystalline in nature and displayed a dual phased ex vivo mucosal permeation pattern. In silico and in vitro physicomechanical quantities revealed OF 2's flexibility, robustness, and compressibility. OF 2 was most stable under controlled environmental humidity, pressure, and temperature conditions in silico and in vitro. OF 2 was potentially non-cytotoxic and biocompatible. Succinctly, this work demonstrated the applicability of a combination of atomistic molecular mechanics and dynamics calculations as well as experimental analyses to the fabrication, screening, optimization, and characterization of drug formulations. Lastly, the fabricated OF 2 formulation can function as a potential alternative for the effective loading and delivery of PYZ.

Structure activity relationships in alkylammonium C12-gemini surfactants used as dermal permeation enhancers.

The purpose of this study was to determine the ability and the safety of a series of alkylammonium C12-gemini surfactants to act as permeation enhancers for three model drugs, namely lidocaine HCl, caffeine, and ketoprofen. In vitro permeation studies across dermatomed porcine skin were performed over 24 h, after pretreating the skin for 1 h with an enhancer solution 0.16 M dissolved in propylene glycol. The highest enhancement ratio (enhancement ratio (ER)=5.1) was obtained using G12-6-12, resulting in a cumulative amount of permeated lidocaine HCl of 156.5 µg cm−2. The studies with caffeine and ketoprofen revealed that the most effective gemini surfactant was the one with the shorter spacer, G12-2-12. The use of the latter resulted in an ER of 2.4 and 2.2 in the passive permeation of caffeine and ketoprofen, respectively. However, Azone was found to be the most effective permeation enhancer for ketoprofen, attaining a total of 138.4 µg cm−2 permeated, 2.7-fold over controls. This work demonstrates that gemini surfactants are effective in terms of increasing the permeation of drugs, especially in the case of hydrophilic ionized compounds, that do not easily cross the stratum corneum. Skin integrity evaluation studies did not indicate the existence of relevant changes in the skin structure after the use of the permeation enhancers, while the cytotoxicity studies allowed establishing a relative cytotoxicity profile including this class of compounds, single chain surfactants, and Azone. A dependence of the toxicity to HEK and to HDF cell lines on the spacer length of the various gemini molecules was found.

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

Human skin not only functions as a permeation barrier (mainly because of 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 especially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters), and nondegradable (polyacrylates) 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 nanosized 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.

Development of paclitaxel-TyroSpheres for topical skin treatment.

A potential topical psoriasis therapy has been developed consisting of tyrosine-derived nanospheres (TyroSpheres) with encapsulated anti-proliferative paclitaxel. TyroSpheres provide enhancement of paclitaxel solubility (almost 4000 times greater than PBS) by effective encapsulation and enable sustained, dose-controlled release over 72 h under conditions mimicking skin permeation. TyroSpheres offer potential in the treatment of psoriasis, a disease resulting from over-proliferation of keratinocytes in the basal layer of the epidermis, by (a) enabling delivery of paclitaxel into the epidermis at concentrations >100 ng/cm(2) of skin surface area and (b) enhancing the cytotoxicity of loaded paclitaxel to human keratinocytes (IC(50) of paclitaxel-TyroSpheres was approximately 45% lower than that of free paclitaxel). TyroSpheres were incorporated into a gel-like viscous formulation to improve their flow characteristics with no impact on homogeneity, release or skin distribution of the payload. The findings reported here confirm that the TyroSpheres provide a platform for paclitaxel topical administration allowing skin drug localization and minimal systemic escape.

Effects of short-term quercetin supplementation on soldier performance.

The purpose was to assess the short-term effects of quercetin supplementation on aerobically demanding soldier performance. In a double-blind crossover study, 16 male soldiers performed 3 days of aerobically demanding exercise under 3 conditions: Baseline (B), Placebo (P), and Quercetin (Q). Day 1 was a treadmill V[Combining Dot Above]O2peak test. Days 2 and 3 were identical, consisting of 75 minutes of loaded treadmill marching (LM) and a subsequent cycling time trial (TT) to complete 200 kJ of work. After B condition, the soldiers consumed 2 energy bars, each containing 0 mg (placebo) or 500 mg of quercetin (1,000 mg·d⁻¹) for 8.5 days. Beginning day 6 of supplementation, the soldiers performed the 3 exercise days. There was a significant (p < 0.05) increase in plasma Q after Q supplementation. Repeated measures analyses of variance revealed no differences after P or Q supplementation as compared with B in V[Combining Dot Above]O2peak (B = 48.9 ± 1.1, P = 49.3 ± 1.1, Q = 48.8 ± 1.2 ml·kg⁻¹·min⁻¹) or TT time (B = 18.4 ± 1.0, P = 18.5 ± 1.1, Q = 18.3 ± 1.0 minutes [mean day 1 and day 2]). The respiratory exchange ratio during LM did not differ across treatments (B = 0.87 ± 0.03, P = 0.87 ± 0.03, Q = 0.86 ± 0.04 [mean day 1 and day 2]). Ratings of perceived exertion were not affected by Q supplementation during the V[Combining Dot Above]O2peak test, LM or TT. Supplementation of 1,000 mg·d⁻¹ of quercetin for 8.5 days had no positive effect on aerobically demanding soldier performance. It is possible that a different dosing regimen, a combination of antioxidants or a different form of quercetin supplementation, may be needed to produce an increase in soldier performance.

Tissue engineered human skin equivalents.

Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed.

A combination of nonionic surfactants and iontophoresis to enhance the transdermal drug delivery of ondansetron HCl and diltiazem HCl.

The present work reports the evaluation of three nonionic ether-monohydroxyl surfactants (C(12)E(1), C(12)E(5,) and C(12)E(8)) as skin permeation enhancers in the transdermal drug delivery of two drugs: ondansetron hydrochloride and diltiazem hydrochloride, formulated as hydrogels. The enhancers are used alone, or in combination with iontophoresis (0.3 mA - 8h). After 1h of pre-treatment with 0.16 M enhancer solutions in propylene glycol (PG), passive and iontophoretic 24 h in vitro studies across dermatomed porcine skin were performed using vertical Franz diffusion cells. Data obtained showed that the nonionic surfactant C(12)E(5) was the most effective permeation enhancer, both for the passive process as well as for samples subjected to iontophoresis, resulting in cumulative amounts of ondansetron HCl after 24h of approximately 93 µg/cm(2) and 336 µg/cm(2), respectively. Data obtained using diltiazem HCl showed a similar trend. The use of the nonionic surfactant C(12)E(5) resulted in higher enhancement ratios (ER) in passive studies, but C(12)E(8) yielded slightly higher values of drug permeated (2678 µg/cm(2)) than C(12)E(5) (2530 µg/cm(2)) when iontophoresis was also employed. Skin integrity studies were performed to assess potential harmful effects on the tissues resulting from the compounds applied and/or from the methodology employed. Skin samples used in permeation studies visualized by light microscopy and Scanning Electron Microscopy (SEM) at different levels of magnification did not show significant morphological and structural changes, when compared to untreated samples. Complementary studies were performed to gain information regarding the relative cytotoxicity of the penetration enhancers on skin cells. MTS assay data using human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) indicated that HEK are more sensitive to the presence of the enhancers than HDF and that the toxicity of these compounds is enhancer molecular weight dependent.