Curcumin nanoparticles as a photoprotective adjuvant.

With rising skin cancer rates and interest in preventing photoaging, adjuvants for sunscreens are in high demand. The potential of curcumin has been posited due to its anti-inflammatory, antioxidant and wound healing properties. In prior studies, curcumin decreased UV-induced inflammation, apoptotic changes in human keratinocytes and dermal fibroblasts, and the expression of matrix metalloproteinases. However, curcumin's utility has been hindered by poor aqueous solubility and rapid degradation in vivo. To overcome these limitations, we synthesized curcumin nanoparticles (curc-np), which offer sustained topical delivery and enhanced bioavailability. Curc-np and controls were applied to the skin of BALB/c mice prior to UVB irradiation. Twenty-four hours later, mice pretreated with curc-np showed less erythema, induration and scale compared to controls. Histopathology showed fewer sunburn cells, and TUNEL assay indicated decreased apoptosis in curc-np treated mice. Immunohistochemistry illustrated less p53 expression in skin pretreated with curc-np. Furthermore, cytokine analysis revealed significantly less IL-6 and significantly greater anti-inflammatory IL-10 in skin of curc-np-treated mice as compared to controls. Taken together, our results reinforce curcumin's established anti-inflammatory effects in the skin and highlight its potential as a photoprotective adjuvant when delivered through nanoparticles. Further investigation alongside sunscreens against UV-induced damage is warranted.

Nitric Oxide Releasing Nanoparticles as a Strategy to Improve Current Onychomycosis Treatments.

Topical antimicrobials are the ideal mode of onychomycosis treatment for efficient drug delivery and avoidance of sytemic effects associated with oral medications. However, high treatment costs, tissue penetration limitations, and low cure rates have continued to pose major challenges. To capitalize on the progress made by topical efinaconazole solution, efinaconazole was combined with inexpensive, previously-characterized nitric oxide releasing nanoparticles (NO-np), which have been shown to offer sustained nitric oxide release over time and enhanced barrier penetration, while exerting broad spectrum antimicrobial and immunomodulating properties. NO-np were combined with efinaconazole in varying concentrations and applied against reference strains of Trichophyton rubrum using a checkerboard method. Results demonstrated synergism of NO-np+efinaconazole against T. rubrum, which is noteworthy given the barriers present in the topical treatment of onychomycosis, and the multiple potential benefits offered by NO-np. Overall, this study illustrates the untapped potential of nanotechnology in the treatment of disorders of the skin, hair, and nails where drug delivery remains a challenge. J Drugs Dermatol. 2018;17(7):717-720.

Topical nitric oxide releasing nanoparticles are effective in a murine model of dermal Trichophyton rubrum dermatophytosis.

Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetration of topical agents. However, systemic antifungals are associated with off-target effects and limited tissue penetration, and antimicrobial resistance is a growing concern. To address this, we investigated topical nitric oxide-releasing nanoparticles (NO-np), which have been used against superficial fungal infections and bacterial abscesses. In addition to enhanced penetration and permeation conferred by nanoparticles, nitric oxide, a broad-spectrum multi-mechanistic antimicrobial agent, offers decreased likelihood of resistance development. In the current study, NO-np inhibited Trichophyton rubrum in vitro, as well as in a murine model of dermal dermatophytosis. In mice, NO-np reduced fungal burden after three days, with complete clearance after seven. Furthermore, NO-np decreased tissue IL-2, 6, 10 and TNFα, indicating earlier attenuation of the host inflammatory response and decreased tissue morbidity. Thus, topical NO-np represent an attractive alternative to systemic therapy against dermal T. rubrum infection.

Phosphorylation of an ERF transcription factor by Arabidopsis MPK3/MPK6 regulates plant defense gene induction and fungal resistance.

Arabidopsis thaliana MPK3 and MPK6, two mitogen-activated protein kinases (MAPKs or MPKs), play critical roles in plant disease resistance by regulating multiple defense responses. Previously, we characterized the regulation of phytoalexin biosynthesis by Arabidopsis MPK3/MPK6 cascade and its downstream WRKY33 transcription factor. Here, we report another substrate of MPK3/MPK6, ETHYLENE RESPONSE FACTOR6 (ERF6), in regulating Arabidopsis defense gene expression and resistance to the necrotrophic fungal pathogen Botrytis cinerea. Phosphorylation of ERF6 by MPK3/MPK6 in either the gain-of-function transgenic plants or in response to B. cinerea infection increases ERF6 protein stability in vivo. Phospho-mimicking ERF6 is able to constitutively activate defense-related genes, especially those related to fungal resistance, including PDF1.1 and PDF1.2, and confers enhanced resistance to B. cinerea. By contrast, expression of ERF6-EAR, in which ERF6 was fused to the ERF-associated amphiphilic repression (EAR) motif, strongly suppresses B. cinerea-induced defense gene expression, leading to hypersusceptibility of the ERF6-EAR transgenic plants to B. cinerea. Different from ERF1, the regulation and function of ERF6 in defensin gene activation is independent of ethylene. Based on these data, we conclude that ERF6, another substrate of MPK3 and MPK6, plays important roles downstream of the MPK3/MPK6 cascade in regulating plant defense against fungal pathogens.

Rapidly Progressive Acute Pustular Secondary Cutaneous Anaplastic Large Cell Lymphoma.

Cutaneous anaplastic large cell lymphoma (ALCL) is an uncommon diagnosis that may either present as a primary cutaneous process or develop secondary to systemic disease. It is imperative to distinguish between these two entities due to differences in treatment recommendations and prognosis. Here, their salient features will be reviewed. It is also important that clinicians recognize atypical clinical morphologies of cutaneous ALCL, including pustular lesions, which may masquerade as infectious or other inflammatory conditions, thereby delaying the onset of treatment. In this report, we present a case of secondary cutaneous ALCL associated with an atypical pustular morphology and an aggressive, fatal course.

J Drugs Dermatol. 2016;15(9):1132-1135.

Bensal HP for Second Intention Healing Following Mohs Micrographic Surgery or Shave Skin Biopsy: An Open-label Pilot Study.

Dermatologists frequently create cutaneous defects that heal by second intention, yet there is no universal protocol for wound care in this setting. Several ointments commonly used for wound healing are not cost effective as they contain known contact allergens, contribute to antimicrobial resistance, and do not enhance the healing process. Recent studies indicate that Bensal HP, a commercially available ointment used for a variety of dermatologic conditions, may be useful for wound healing; although clinical data is currently limited. In this single-center open-label pilot study, Bensal HP was evaluated for second intention healing over 8 weeks following either Mohs micrographic surgery or shave skin biopsy in 20 patients. Results indicate that Bensal HP is effective for second intention healing as demonstrated by increased Global Assessment of Efficacy scores and decreased wound measurements, with 16 patients achieving full closure. Patient symptoms overall improved over the study period, and Bensal HP was well tolerated with no adverse effects associated with its use. By providing critical data regarding the safety and efficacy of Bensal HP, this study may provide useful information to guide further assessment in future large-scale comparative wound healing studies.

J Drugs Dermatol. 2016;15(10):1197-1202.

Bensal HP Attenuates the Inflammatory Response in Hair Shaving Associated Dermatitis.

Shaving is an ubiquitous practice, and cutaneous irritation and inflammation are common sequelae, which may be worsened by underlying skin conditions or poor hair removal techniques. Moisturizing shaving creams and aftershaves are available to help maintain or restore the epidermal barrier; however, many continue to suffer from post-shave redness, itching, and pain. To reduce post-shave inflammation, some products have included botanical and other natural ingredients, which are often favored by consumers. We evaluated Bensal HP, an ointment containing 3% oak bark extract, 3% salicylic acid, and 6% benzoic acid, which has documented anti-inflammatory and antimicrobial properties, in a murine model of shave irritation to determine whether it would be useful in this clinical setting. Shaving dermatitis was simulated using a depilatory agent and electric clippers, and the shaved area was photographed and treated with Bensal HP daily for four days. Compared to untreated controls, mice treated with Bensal HP experienced a visible reduction in skin irritation and inflammation. These findings were mirrored on histology, as Bensal HP-treated areas demonstrated increased epidermal integrity and decreased dermal inflammatory infiltrate compared to untreated skin. Using immunohistochemistry, fewer neutrophils and macrophages were noted, and cytokine analysis also revealed decreased IL-6 in Bensal HP-treated skin at 24 and 96 hours after shaving. These results highlight the potential of Bensal HP as an anti-inflammatory treatment for shave irritation. Given the product's application against a variety of inflammatory and infectious skin disorders, its use against shave irritation may also improve comorbid skin conditions, such as pseudofolliculitis barbae.

J Drugs Dermatol. 2016;15(7):836-840.

S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology.

Nitric oxide (NO), an essential agent of the innate immune system, exhibits multi-mechanistic antimicrobial activity. Previously, NO-releasing nanoparticles (NO-np) demonstrated increased antimicrobial activity when combined with glutathione (GSH) due to formation of S-nitrosoglutathione (GSNO), a transnitrosylating agent. To capitalize on this finding, we incorporated the thiol-containing ACE-inhibitor, captopril, with NO-np to form SNO-CAP-np, nanoparticles that both release NO and form S-nitrosocaptopril. In the presence of GSH, SNO-CAP-np demonstrated increased transnitrosylation activity compared to NO-np, as exhibited by increased GSNO formation. Escherichia coli and methicillin-resistant Staphylococcus aureus were highly susceptible to SNO-CAP-np in a dose-dependent fashion, with E. coli being most susceptible, and SNO-CAP-np were nontoxic in zebrafish embryos at translatable concentrations. Given SNO-CAP-np's increased transnitrosylation activity and increased E. coli susceptibility compared to NO-np, transnitrosylation rather than free NO is likely responsible for overcoming E. coli's resistance mechanisms and ultimately killing the pathogen. FROM THE CLINICAL EDITOR: This team of authors incorporated the thiol-containing ACE-inhibitor, captopril, into a nitric oxide releasing nanoparticle system, generating nanoparticles that both release NO and form S-nitrosocaptopril, with pronounced toxic effects on MRSA and E. coli in the presented model system.