The Johns Hopkins University

Other

The University of North Carolina at Chapel Hill

Reprotect, Inc.

Richard A Cone

Justin Scot Hanes

Laura M Ensign

Thomas R Moench

Katharina Maisel

Kevin J Whaley

Samuel K Lai

Durai Babu Subramani

Arthi Kannan

Craig W Hendrix

Ying-Ying Wang

Edward Fuchs

Bing Yang

Justin Mccallen

Kenetta Nunn

Randy Wills

Kennetta Nunn

Methods and materials for treating bacterial vaginosis ('BV') are provided. Cervicovaginal secretions (“CVS”) from a woman with vaginal microbiota dominated (>50%) by one of the species oftypically found in the human vagina, e.g., is transplanted to women with BV as a method for restoring beneficial vaginal microbial communities and/or increasing resistance to sexually transmitted disease. Efficacy can be enhanced, or the properties of the endogenous CVS improved, through administration of an acidifying agent such as lactic acid. The examples demonstrate the role of healthy CVS in disease resistance, and the effect of pH on CVS properties. The examples also describe the collection and transplantation of healthy beneficial CVS into women at risk for, or after treatment for, BV.

CVS transplantation for treatment of bacterial vaginosis

The presently-disclosed subject matter relates to antibodies, compositions, and methods for inhibiting and treating virus infection in the respiratory tract and virus transmission through the respiratory tract. In particular, the presently-disclosed subject matter relates to inhibiting and treating virus infection in a subject using compositions and antibodies that trap viruses in mucus of the respiratory tract, thereby inhibiting transport of virus across or through mucus secretions.

Compositions and methods for inhibiting pathogen infection

Hypotonic microbicidal compositions including an antimicrobial, such as an antiviral compound, and a pharmaceutically acceptable carrier in a solution formulation having hypotonic osmolarity have been developed for administration rectally to the gastrointestinal mucosa. In a preferred embodiment for use in preventing or decreasing HIV infection, the microbicidal is tenofovir, or a prodrug or derivative thereof. The formulations may include additional agents such as surfactants to enhance cleansing, buffers, or preservatives. Polymers may be included for osmolarity as well as comfort.

Hypotonic microbicidal formulations and methods of use

Hypotonic formulations of hydrogel forming polymers, preferably poloxamers, have been developed for enhanced delivery through mucosa of therapeutic, diagnostic, prophylactic or other agents, to epithelial tissues, especially those having a mucosal coating. The polymers are administered at a concentration above, at or less than their critical gelling concentration (CRC) under isotonic conditions. The hypo tonicity of the formulation is adjusted so that the polymer gels at the lower concentration. A Poloxamer gel administered into the vagina or colorectal at its CRC will form a 'plug' of gel in the lumen.

Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces

Mucus penetrating particles (MPPs) include one or more core polymers, one or more therapeutic, prophylactic and/or diagnostic agents; and one or more surface modifying agents. The surface modifying agents coat the surface of the particle in a sufficient density to enhance the diffusion of the modified nanoparticles throughout the mucosa, relative to equivalent nanoparticles that are not surface modified. Nanoparticles can be sufficiently densely coated with poly(ethylene glycol) (PEG) with a molecular weight of from 10 kD to 40 kD or greater coated with a surface density from about 0.1 to about 100 molecules/100 nm, preferably from about 0.5 to about 50 molecules/100 nm, more preferably from about 0.9 to about 45 molecules/100 nm.

Mucus penetrating particles with high molecular weight and dense coatings

Hypotonic formulations of hydrogel forming polymers, preferably poloxamers, have been developed for enhanced delivery through mucosa of therapeutic, diagnostic, prophylactic or other agents, to epithelial tissues, especially those having a mucosal coating. The polymers are administered at a concentration above, at or less than their critical gelling concentration (CGC) under isotonic conditions. The hypotonicity of the formulation is adjusted so that the polymer gels at the lower concentration. A Poloxamer gel administered into the vagina or colorectum at its CGC will form a 'plug' of gel in the lumen.

Methods and materials for treating bacterial vaginosis ('BV') are provided. Cervicovaginal secretions ('CVS') from a woman with-dominated (&#x3e;50%) vaginal microbiota is transplanted to women with BV as a method for restoring beneficial vaginal microbial communities and/or increasing resistance to sexually transmitted disease. Efficacy can be enhanced, or the properties of the endogenous CVS improved, through administration of an acidifying agent such as lactic acid. The examples demonstrate the role of healthy CVS in disease resistance, and the effect of pH on CVS properties. The examples also describe the collection and transplantation of healthy beneficial CVS into women at risk for, or after treatment for, BV.

The presently-disclosed subject matter relates to antibodies, compositions, and methods for inhibiting and treating pathogen infection and providing contraception. In particular, the presently-disclosed subject matter relates to inhibiting and treating pathogen infection and providing contraception in a subject using compositions and antibodies capable of trapping pathogens or sperm in mucus, thereby inhibiting transport of pathogens or sperm across mucus secretions. The subject matter further relates to methods for monitoring the effectiveness of vaccines by detecting antibodies capable of trapping pathogens in mucus.

Hypotonic microbicidal compositions including an antimicrobial, such as an antiviral compound, and a pharmaceutically acceptable carrier in a solution formulation having hypotonic osmolarity have been developed for administration rectally to the gastrointestinal mucosa. In a preferred embodiment for use in preventing or decreasing HIV infection, the microbiocidal is tenofovir, or a prodrug or derivative thereof. The formulations may include additional agents such as surfactants to enhance cleansing, buffers, or preservatives. Polymers may be included for osmolarity as well as comfort.

Hypotonic formulations were evaluated for delivering water-soluble drugs and for drug delivery with muco-inert (that is, non-adhesive) mucus-penetrating nanoparticles (MPP). Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface, including deep into the vaginal folds. Minimally hypotonic formulations, preferably ranging from 20-220 mOsm/kg, provided rapid and uniform delivery of MPP to the entire vaginal surface, with minimal risk of epithelial toxicity. Data also show that there is a higher osmolality in the colon, such that vehicles with an osmolality above that of blood plasma (generally considered isotonic at &#x2dc;300 mOsm/kg), still lead to improvements in distribution in the colon due to rapid, osmotically-induced fluid absorption. The range for improved colon distribution with a hypotonic vehicle in the colon is &#x2dc;20 mOsm/kg-450 mOsm/kg.

Nanoparticle formulations with enhanced mucosal penetration

The present invention provides improved rim designs for diaphragms or any similar intravaginal device and methods for producing same. The rim designs of the present invention improve, among other characteristics of the rim, structural durability, manufacturability, ease of insertion, comfort in use, and ease of removal of intravaginal devices. These designs incorporate one or more recesses in the inner portion of a rim piece that provide an attachment site for a separate dome piece. Attachment within a recess shields the exposed outer edge of the dome material from contact with epithelial surfaces and improves comfort and safety. In certain embodiments of the invention, a thinned inner portion of the rim serves as a handle that can be easily grasped by a finger to remove the device from the vagina. These devices are useful in providing a protective cervical barrier for contraception and disease prevention, to deliver beneficial agents, and as a means to collect and remove substances from the vagina.

Intravaginal device with improved rim designs and methods of making same

The present invention reveals a device, a kit and a method for simultaneously delivering and distributing at least one beneficial agent to both the cervical and vaginal lumen sides of a vagina. The device is made of a flexible circular rim and a flexible dome. The device can exist in either a relaxed state or in a compressed state. In the compressed state, pouches are formed for carrying and delivering the beneficial agent to both the cervical and vaginal lumen sides of the vagina.

Growing community of inventors

Baltimore, MD, United States of America

Richard A Cone