Characterization of bound water in skin hydrators prepared with and without a 3D3P interpenetrating polymer network.

BACKGROUND: Hyaluronic acid (HA) has been considered the gold standard ingredient for improving skin hydration and combating age-related effects, however it is an inefficient polymer with inconsistent results partially due to its poor skin penetration, surface deposition, and rapid degradation. Herein we report the synthesis and in vitro characterization of a newly developed, topical super-humectant with the goal of attracting and binding water molecules more efficiently than traditional, cosmetic-grade forms of HA. METHODS: A modified interpenetrating polymer network (IPN) was developed using three polymers into a three-dimensional formation (3D3P) for entrapping HA and water. This 3D3P-IPN functions as a super-humectant, attracting and binding water molecules more efficiently than the traditional cosmetic-grade forms of HA. We compare 3D3P-IPN serum samples to a traditional commercial benchmark product of similar ingredients using microscopic analysis, rheology, Karl Fischer (KF) titration, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and dynamic vapor sorption (DVS) techniques. RESULTS: The 3D3P-IPN samples appeared to bind water tighter than the benchmark sample as evidenced by maximum endpoints of endotherms occurring at significantly higher temperatures. The DVS results further confirm this speculation as the 3D3P-IPN samples lost approximately 10% less water up to 35% RH than the benchmark. The 3D3P-IPN samples also absorbed more water as the humidity level increased,demonstrating superior humectant properties. KF titration indicated that all three samples had similar water concentrations; however, TGA results demonstrated that the benchmark (a viscous, humectant-rich hydrating masque) did not have much bound water. CONCLUSION: Through the synthesis of a 3D3P-IPN using simplified methods, we were able to increase the water-binding and HA-delivery capabilities of a thin serum. This 3D3P-IPN serum has potential to deliver more hydration to the skin's surface compared to traditional HA formulations.

Efficacy and Tolerability of a Twice-Daily, Three-Step Men's Skincare Regimen in Improving Overall Skin Quality and Reducing Shave-Related Irritation.

More men are beginning to take advantage of opportunities to improve the health and appearance of their skin; however, the effectiveness of men's skincare regimens has not been well studied. The authors investigated the efficacy and tolerance of a twice-daily, three-step men's skincare regimen in improving skin appearance and reducing shave-related issues. Twenty-nine men who used a wet-shaving method completed a specific, three-step, twice-daily facial regimen-a Shave Cleanser, a Post-Shave Treatment, and Day Protection-in place of their usual routine for 4 weeks. This skincare regimen produced significant improvements in tactile smoothness, clarity, radiance, and pore size at weeks 2 and 4 and in fine lines, razor burn, and photodamage at week 4 (P<.05). Significant improvements were seen in the appearance of nicks/cuts and folliculitis of the face and neck after weeks 2 and 4 (P<.05). Mean change in the moisture content of the stratum corneum was significant at week 4 (P<.05). The majority of men provided positive self-assessments and indicated an interest in continuing this regimen.

Efficacy of hexapeptide-7 on menopausal skin.

Due to a reduction in estrogen levels peri- and post-menopausal skin exhibit a specific phenotype characterized by reduced thickness, reduced elasticity and increased dryness. Loss of these elements results in increased skin wrinkling and skin sagging. In addition, it is well documented that reduced estrogen levels also negatively impacts dermal wound healing. As a result we tested the hypothesis that molecules capable of stimulating and accelerating wound healing can supplement the skin's diminished activities produced by reduced estrogen. Heptapeptide-7, a fragment of a well-characterized wound healing peptide (HB-107), was found to stimulate keratinocyte proliferation and migration and induce collagen synthesis. Microarray analysis of Heptapeptide-7-treated dermal keratinocytes revealed an up-regulation of cell division, growth factor and extracellular matrix genes. Validation of this approach was seen in a clinical study of 32 women (mean age 54) in which forehead wrinkles and skin texture were improved with the application of this peptide fragment.

Efficacy of a twice-daily, 3-step, over-the-counter skincare regimen for the treatment of acne vulgaris.

BACKGROUND: Acne vulgaris (acne) is the most common skin disorder producing physical and emotional scars that can persist for years. An estimated 83% of acne sufferers self-treat, but there is lack of studies documenting the effectiveness of over-the-counter (OTC) acne treatment products. OBJECTIVE: This study was conducted to determine the effectiveness of an OTC, 3-step, anti-acne skincare regimen in treating acne and improving the appearance of red/inflamed facial skin. METHODS: This 6-week, open-label clinical study included both genders aged between 12 and 35 years with mild-to-moderate acne. All subjects were required to have an acne score of 1-3 (Cook's acne grading scale: 0=clear to 7=very severe) and a moderate redness score of ≥2 (0=none and 4=severe). Subjects completed a 3-step facial treatment regimen every morning and evening using an OTC cleanser, toner, and acne treatment. Evaluations for effectiveness and safety were done at baseline and weeks 2, 4, and 6 using digital photographs (Visia-CR® digital imaging system) of the face and analyzed using Image-Pro® software for the grading of acne, red/inflamed skin, and the number and type of lesions. RESULTS: Thirty subjects (12 males and 18 females) were enrolled (mean age of 19 years; range 12-34 years). This skincare regimen resulted in statistically significant improvements in acne grading scores after 2 weeks of use, with mean scores continuing to improve after 4 and 6 weeks of use (P<0.001). Statistically significant improvements from baseline in red/inflamed skin, open and closed comedones, and papules were detected at all time points and for nodules at week 6, compared to their respective baselines (P<0.05). CONCLUSION: This clinical study demonstrated the effectiveness of an OTC 3-step, anti-acne skincare regimen in significantly improving acne and the overall appearance of skin in the majority of subjects who had mild-to-moderate acne.

Cationic antimicrobial peptides - an update.

Cationic antimicrobial peptides play a very important role in nature as a first line of defence against attack and damage. However, their application to the clinic has not been very encouraging to date. There are indications that the barriers to their success may now be eroding with companies developing peptides to be more stable, cost effective and targeted to specific indications. These include systemic infectious disease, acne, vaginitis, wound infection and inflammation. In addition, the use of such peptides as modulators of innate immunity in the treatment of infectious disease and inflammation has added a further dimension to the field.

Potential therapeutic application of host defense peptides.

Host defense peptides (HDPs) are relatively small, mostly cationic, amphipathic, and of variable length, sequence, and structure. The majority of these peptides exhibit broad-spectrum antimicrobial activity and often activity against viruses and some cancer cell lines. In addition, HDPs also provide a range of immunomodulatory activities related to innate immunity defense, inflammation, and wound healing. The development of these multi-faceted molecules and their bioactivities into clinically important therapeutics is being pursued using a number of different approaches. Here we review the role of HDPs in nature and application of this role to the development of novel therapeutics.

Host defense peptides for use as potential therapeutics.

The ongoing emergence of bacterial strains resistant to multiple classes of antimicrobial agents continually exerts pressure on researchers to develop novel molecules and novel approaches to combat these bacterial pathogens. One such approach is the use of topical agents to prevent or treat infections of exposed and accessible tissue. These surfaces are primarily protected in humans by innate immunity, and a significant part of this system consists of the activities of host-defense peptides. Recently, these molecules have been demonstrated to exhibit a wide range of defense-targeted activities, including antimicrobial efficacy. This review details the role and activities of these peptides, and examines their applicability as development candidates for use as topical antibiotics.

Cosmeceuticals and peptides.

In nature, the majority of chemical reactions, biological responses, and regulatory processes are modulated in some part by specific amino acid sequences. The transfer of these interactive sequences and the biological activities they induce to short, stable, and readily synthesized peptides has created a diverse new field of modulating molecules applicable to dermatology and skin care industries. Areas such as inflammation, pigmentation, cell proliferation and migration, angiogenesis, innate immunity, and extracellular matrix synthesis have yielded peptide candidates for application to this area.

Antimicrobial peptides: therapeutic potential.

A significant component of the innate immune system of a wide variety of animals and plants is arbitrated by cationic host defence peptides. In man, these peptides, in addition to exhibiting a direct antimicrobial activity, seems to provide a range of non-antimicrobial bioactivities related to defence, inflammation and wound healing. Despite the fact that such peptides have so far failed to reach the market, there are continued initiatives to advance such potential therapeutics to, and through, the clinic. The reasons behind such initiatives include: reduced manufacturing costs for peptides; allowing entry into therapeutic areas previously inaccessible due to cost; the continued identification of previously unknown bioactivities of such peptides; and the resurgence of interest in peptide therapeutics. As a result, clinical programmes based on cationic host defence peptides exist in the areas of infection, dermatology, cancer and inflammation. The probability of clinical success for host defence peptide-based therapeutics is on the rise as options for a wider range of clinical indications emerge.

Antimicrobial peptide therapeutics for cystic fibrosis.

Greater than 90% of lung infections in cystic fibrosis (CF) patients are caused by Pseudomonas aeruginosa, and the majority of these patients subsequently die from lung damage. Current therapies are either targeted at reducing obstruction, reducing inflammation, or reducing infection. To identify potential therapeutic agents for the CF lung, 150 antimicrobial peptides consisting of three distinct structural classes were screened against mucoid and multidrug-resistant clinical isolates of P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Staphylococcus aureus. Five peptides that retained potent antimicrobial activities in physiological salt and divalent cation environment were further characterized in vivo using a rat chronic lung infection model. All animals were inoculated intratracheally with 10(4) P. aeruginosa mucoid PAO1 cells in agar beads. Three days following inoculation treatment was initiated. Animals were treated daily for 3 days with 100 microl of peptide solution (1 mg/ml) in 10 mM sodium citrate, which was deposited via either intratracheal instillation or aerosolization. Control animals received daily exposure to vehicle alone. At the end of the treatment the lungs of the animals were removed for quantitative culture. Four peptides, HBCM2, HBCM3, HBCPalpha-2, and HB71, demonstrated significant reduction in Pseudomonas bioburden in the lung of rats. Further in vivo studies provided direct evidence that anti-inflammatory activity was associated with three of these peptides. Therefore, small bioactive peptides have the potential to attack two of the components responsible for the progression of lung damage in the CF disease: infection and inflammation.

HB-107, a nonbacteriostatic fragment of the antimicrobial peptide cecropin B, accelerates murine wound repair.

Antimicrobial peptides are essential to innate host defense as effectors of pathogen clearance and can modify host cell behaviors to promote wound repair. While these two functions appear interrelated, it is unclear whether the ability to aid in wound repair requires inherent antimicrobial function. We hypothesized that the influence of antimicrobial peptides on wound repair is not dependent on antimicrobial function. To explore this, we analyzed the microbial killing activity of peptide fragments and correlated this with the ability to influence wound repair in mice. HB-107, a peptide lacking antimicrobial activity and originally derived from the antimicrobial cecropin B, showed up to 64 percent improvement in wound repair compared to scrambled peptide and vehicle controls, an effect comparable to treatment with recombinant human platelet-derived growth factor-BB (formulated as Regranex). Wounds treated with HB-107 showed keratinocyte hyperplasia and increased leukocyte infiltration. Furthermore, HB-107 stimulated interleukin-8 secretion from cultured endothelial cells, an effect that may explain the increase in leukocyte migration. These findings confirm that antimicrobial peptides can function as effectors of cutaneous wound repair. Moreover, this study furthers our understanding of antimicrobial peptides by showing that their wound repair properties can be independent of antimicrobial function.