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Atopic Dermatitis (AD) is characterized by skin barrier disruption and an aberrant immune response. Doxycycline are tetracycline antibiotics broadly used systemically to treat inflammatory-dermatologic conditions. Several studies have shown doxycycline have anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. It is our hypothesis that daily application of a novel Doxycycline topical formulation in AD subjects will reduce severity of the disease, by blocking cutaneous proteases activity and restoring skin barrier function and inflammation. To test this hypotehsis we performed a proof of concept, open-label clinical study. Subjects enrolled in the study (n=15) applied NanoDOX® Hydrogel 1% daily for four weeks on a chosen eczematous area. Investigational drug was well tolerated, no local or systemic adverse events due to investigational drug were reported. Notably, a significant clinical improvement was observed based on a modified Eczema Area & Severity Index (EASI) score of the treated area from start of treatment to 14 and 28 days post treatment (p

It is widely believed that protection against acquisition of HIV or SIV infection requires anti-envelope (anti-Env) antibodies, and that cellular immunity may affect viral loads but not acquisition, except in special cases. Here we provide evidence to the contrary. Mucosal immunization may enhance HIV vaccine efficacy by eliciting protective responses at portals of exposure. Accordingly, we vaccinated macaques mucosally with HIV/SIV peptides, modified vaccinia Ankara–SIV (MVA-SIV), and HIV-gp120–CD4 fusion protein plus adjuvants, which consistently reduced infection risk against heterologous intrarectal SHIV(SF162P4) challenge, both high dose and repeated low dose. Surprisingly, vaccinated animals exhibited no anti-gp120 humoral responses above background and Gag- and Env-specific T cells were induced but failed to correlate with viral acquisition. Instead, vaccine-induced gut microbiome alteration and myeloid cell accumulation in colorectal mucosa correlated with protection. Ex vivo stimulation of the myeloid cell–enriched population with SHIV led to enhanced production of trained immunity markers TNF-α and IL-6, as well as viral coreceptor agonist MIP1α, which correlated with reduced viral Gag expression and in vivo viral acquisition. Overall, our results suggest mechanisms involving trained innate mucosal immunity together with antigen-specific T cells, and also indicate that vaccines can have critical effects on the gut microbiome, which in turn can affect resistance to infection. Strategies to elicit similar responses may be considered for vaccine designs to achieve optimal protective efficacy.

Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.

Polymer/layered silicate nanocomposite thin films were developed as clear, transparent coatings. Laponite‐S, which is a synthetic layered clay, was dispersed in a polyethylene oxide matrix and solution cast onto glass slides for further testing. Rheological properties, wear abrasion resistance, and scratch resistance were tested for each sample to examine the nanoparticle dispersion effects on the materials' properties. In this study, we identify and characterize the materials to be used, establish the appropriate conditions for the preparation of polymer/Laponite nanocomposite dispersions, illustrate methods for the development of PEO/Laponite‐S films, and characterize the films. Results on the rheological behavior of PEO‐silicate nanocomposites as a function of Laponite solids loading and PEO concentration, as well as some preliminary wear abrasion properties of the films are presented in this study.

TM ; Dual de- tection; Dry powder; Inhalation Abstract A stability indicating HPLC assay with UV detection was developed for the simultaneous quantification of Gentamicin Sulfate and L-leucine from NanoGENT™ dry powder for inhalation. In order to support the development of the NanoGENT™ (dry powder Gentamicin Sulfate for inhalation) the assay was created to allow simultaneous detection of the active pharmaceutical ingredient (Gentamicin Sulfate) and the primary excipient (L-leucine). In order to quantify Gentamicin Sulfate by UV detection derivatization was required. The assay resolved L-leucine from all four Gentamicin Sulfate peaks and all four Gentamicin Sulfate peaks from each other with a reversed phase isocratic assay. Once developed the assay was validated in accordance with regulatory guidance in order to support regulatory approval of the NanoGENT™ dry powder inhalation formulation. The validation data indicated that the dual detection assay meets or exceeded all criteria for use as a stability indicating assay. Orally inhaled therapeutics are a mainstay in the treatment of asthma and COPD and is growing rapidly in the treatment of other pulmonary and systemic indications. The growth of orally inhaled therapeutics to treat atypical indications has broadened beyond vaccines and insulin to include biological threats. This growth has exacerbated the fact that there are currently a minimal number of GRAS excipients for inhalation delivery (1). Further, the excipients that are considered GRAS do not span the range of physical chemical properties that are often required for formulations of a material for delivery to the lungs.