Angelo Landriscina

Biodegradable chitosan nanoparticles in drug delivery for infectious disease

Increasing rates of antimicrobial resistance have left a significant gap in the standard antimicrobial armament. Nanotechnology holds promise as a new approach to combating resistant microbes. Chitosan, a form of deacetylated chitin, has been used extensively in medicine, agriculture and industry due to its ease of production, biocompatibility and antimicrobial activity. Chitosan has been studied extensively as a main structural component and additive for nanomaterials. Specifically, numerous studies have demonstrated its potent microbicidal activity and its efficacy as an adjuvant to vaccines, including mucosally administered vaccines. In this review, we present fundamental information about chitosan and chitosan nanoparticles as well as the most recent data about their antimicrobial mechanism and efficacy as a nanotechnology-based drug delivery system.

Trichophyton rubrum is Inhibited by Free and Nanoparticle Encapsulated Curcumin by Induction of Nitrosative Stress after Photodynamic Activation

Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use against Trichophyton rubrum, a dermatophytic fungus with increasing incidence and resistance, has not been well characterized. Our aim was to evaluate the mechanism of action of aPI against T. rubrum using curcumin as the PS in both free and nanoparticle (curc-np) form. Nanocarriers stabilize curcumin and allow for enhanced solubility and PS delivery. Curcumin aPI, at optimal conditions of 10 μg/mL of PS with 10 J/cm2 of blue light (417 ± 5 nm), completely inhibited fungal growth (p<0.0001) via induction of reactive oxygen (ROS) and nitrogen species (RNS), which was associated with fungal death by apoptosis. Interestingly, only scavengers of RNS impeded aPI efficacy, suggesting that curcumin acts potently via a nitrosative pathway. The curc-np induced greater NO• expression and enhanced apoptosis of fungal cells, highlighting curc-np aPI as a potential treatment for T. rubrum skin infections.

Silver Sulfadiazine Retards Wound Healing in Mice via Alterations in Cytokine Expression

Methods: Thermal burns were induced on the dorsal surface of BALB/c mice; mice were split into two groups: untreated control (n=56) and SSD-treated (n=46) (50μL of 1% SSD cream per wound daily). Daily photographs and Image J software were used to asses change in wound area relative to day 0. Histologic samples were stained using hematoxylin and eosin (H&E), Masson’s trichrome, ionized calcium-binding adapter molecule-1(IBA-1) and myeloperoxidase (MPO) to visualize morphology, collagen deposition, macrophages and neutrophils respectively. Burn wounds were harvested for cytokine analysis (n= 10 wounds, 5 animals per group) and tissue samples were analyzed in duplicate for cytokine expression using Mouse Cytokine Antibody Array and cytokine signal intensity was measured using Quantity One Software.

Biafine topical emulsion accelerates excisional and burn wound healing in mice

Macrophages play a fundamental role in wound healing; therefore, employing a strategy that enhances macrophage recruitment would be ideal. It was previously suggested that the mechanism by which Biafine® topical emulsion improves wound healing is via enhanced macrophage infiltration into the wound bed. The purpose of this study was to confirm this observation through gross and histologic assessments of wound healing using murine full-thickness excisional and burn wound models, and compare to common standards, Vaseline and silver sulfadiazine (SSD). Full-thickness excisional and burn wounds were created on two groups of 60 mice. In the excisional arm, mice were divided into untreated control, Biafine, and Vaseline groups. In the burn arm, mice were divided into untreated control, Biafine, and SSD groups. Daily treatments were administered and healing was measured over time. Wound tissue was excised and stained to appropriately visualize morphology, collagen, macrophages, and neutrophils. Collagen deposition was measured and cell counts were performed. Biafine enhanced wound healing in murine full-thickness excisional and burn wounds compared to control, and surpassed Vaseline and SSD in respective wound types. Biafine treatment accelerated wound closure clinically, with greater epidermal/dermal maturity, granulation tissue formation, and collagen quality and arrangement compared to other groups histologically. Biafine application was associated with greater macrophage and lower neutrophil infiltration at earlier stages of healing when compared to other study groups. In conclusion, Biafine can be considered an alternative topical therapy for full-thickness excisional and burn wounds, owing to its advantageous biologically based wound healing properties.

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.

Nitric Oxide–Releasing Nanoparticles as an Antimicrobial Therapeutic

Abstract The development of new antimicrobial agents has fallen behind microbial drug resistance, posing a significant challenge for combating infectious disease. Nanotherapeutics have revolutionized antimicrobial therapy, providing new mechanisms to combat microbial resistance. Nitric oxide (NO), a simple gaseous molecule with ubiquitous biological activity, represents one such strategy as its antimicrobial properties are well described. Harnessing this potential has proven difficult given the lack of effective delivery vehicles. However, this challenge has been overcome by the generation of a nanoparticulate system capable of generating physiologic concentrations of NO over time. The efficacy of these platforms against bacteria and fungi has been shown in a variety of studies. Here, we review the role of NO-releasing nanoparticulate platforms as an antimicrobial therapeutic agent.

Identifying new biologic targets in atopic dermatitis (AD): A retrospective histologic analysis

To the Editor: Atopic dermatitis (AD) is a chronic inflammatory disorder associated with significant morbidity in both childhood and adulthood, with increased prevalence and incidence over the past 3 decades. There are limited treatment options for AD, with few addressing pruritus. Pruritogenic mediators, including 5-lipoxygenase, leukotriene B4, interleukin (IL)-2, and matrix metalloproteinase (MMP)-7, have not been characterized within this