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Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA‐NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA‐NP decreased IL‐6 and MCP‐1 in UVB‐stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA‐NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL‐lpr lupus murine model, twice weekly treatment of lesions with topical AEA‐NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA‐NP to commonly involved areas on MRL‐lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA‐1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential. [ABSTRACT FROM AUTHOR]

Background Curcumin, a naturally occurring anti-inflammatory compound, has shown promise in pre-clinical studies to treat erectile dysfunction (ED) associated with type-1 diabetes. However, poor bioavailability following oral administration limits its efficacy. The present study evaluated the potential of topical application of curcumin-loaded nanoparticles (curc-np) to treat ED in a rat model of type-2 diabetes (T2D). Aim Determine if topical application of curc-np treats ED in a T2D rat model and modulates expression of inflammatory markers. Methods Curc-np (4 mg curcumin) or blank nanoparticles were applied every 2 days for 2 weeks to the shaved abdomen of 20-week-old Zucker diabetic fatty male rats ( N = 5 per group). Lean Zucker diabetic fatty male rat controls were treated with blank nanoparticles ( N = 5). Penetration of nanoparticles and curcumin release were confirmed by 2-photon fluorescence microscopy and histology. Erectile function was determined by measuring intracorporal pressure (ICP) normalized to systemic blood pressure (ICP/BP) following cavernous nerve stimulation. Corporal tissue was excised and reverse transcription and quantitative polymerase chain reaction used to determine expression of the following markers: nuclear factor (NF)-κβ, NF-κβ-activating protein ( Nkap ), NF erythroid 2-related factor-2, Kelch-like enoyl-CoA hydratase-associated protein-1, heme oxygenase-1 ( HO-1 ), variable coding sequence-A1, phosphodiesterase-5, endothelial and neuronal nitric oxide synthase, Ras homolog gene family member A, and Rho-associated coiled-coil containing protein kinases-1 and -2. Outcomes Erectile function by determination of ICP/BP and expression of molecular markers in corporal tissue by RT-qPCR. Results Nanoparticles penetrated the abdominal epidermis and persisted in hair follicles for 24 hours. Curc-np-treated animals exhibited higher average ICP/BP than animals treated with blank nanoparticles at all levels of stimulation and this was statistically significant ( P < .05) at 0.75 mA. In corporal tissue, Nkap expression decreased 60% and heme oxygenase-1 expression increased 60% in curc-np- compared to blank nanoparticle–treated animals. ICP/BP values inversely correlated with Nkap and directly correlated with HO-1 expression levels. Clinical Translation These studies demonstrate the potential for topical application of curc-np as a treatment for ED in T2D patients. Conclusions The T2D animal model of ED represents a more prevalent disease than the more commonly studied type-1 diabetes model. Although there is improved erectile response in curc-np-treated animals, only at the lower levels of stimulation (0.75 mA) was this significant compared to the blank nanoparticle–treated animals, suggesting more studies are needed to optimize protocols and evaluate toxicity. Topical application of curc-np to a rat model of T2D can systemically deliver curcumin, treat ED, and modulate corporal expression of inflammatory markers. Draganski A, Tar MT, Villegas G, et al. Topically Applied Curcumin-Loaded Nanoparticles Treat Erectile Dysfunction in a Rat Model of Type-2 Diabetes. J Sex Med 2018;15:645–653. [ABSTRACT FROM AUTHOR]

Background: Bacteria, particularly in the biofilm state, may be implicated in the pathogenesis of chronic rhinosinusitis (CRS) and enhance antibiotic resistance. Nitric oxide (NO) is a gaseous immunomodulator with antimicrobial activity and a short half‐life, complicating achievement of therapeutic concentrations. We hypothesized that a novel microparticle‐based delivery platform, which allows for adjustable release of NO, could exhibit potent antibacterial effects. Methods: Porous organosilica microparticles (SNO‐MP) containing nitrosylated thiol groups were formulated. Dissociation of the nitrosothiol groups generates NO at body temperature. The susceptibility of bacterial isolates from CRS patients to SNO‐MP was evaluated through a colony forming unit (CFU) assay. Serial dilutions of SNO‐MP in triplicate were incubated with isolates in suspension for 6 hours followed by plating on tryptic soy agar and overnight incubation followed by CFU quantification. Statistical analysis was performed with SPSS using one‐way analysis of variance with Bonferroni correction. Results: SNO‐MP displayed antibacterial activity against gram‐positive (methicillin‐resistant and ‐sensitive Staphylococcus aureus) and gram‐negative (Pseudomonas aeruginosa, Enterobacter aerogenes, and Proteus mirabilis) isolates. SNO‐MP induced dose‐dependent reductions in CFU across all strains. Compared with controls and blank nanoparticles, SNO‐MP (10 mg/mL) induced a 99.99%‐100% reduction in CFU across all isolates, equivalent to a 5–9 log kill (p < 0.005). There was no statistically significant difference in CFU concentration between controls and blank microparticles. Conclusion: SNO‐MP demonstrates potent bactericidal effect against antibiotic‐resistant CRS bacterial strains. [ABSTRACT FROM AUTHOR]