Abstract: Controlled release microparticular formulations for the delivery of active agents, especially for treatment of eye diseases or disorders, such as glaucoma, have been developed. These provide release of the active agent, such as a hydrophilic carbonic anhydride inhibitor, for an effective period of time such as a least one month after injection into the eye for treatment of glaucoma.

Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder that affects more than 1 million individuals in the USA. Described herein are nanoparticle mucus penetrating formulations for administration of drugs for improved mucosal distribution and tissue penetration such as in the treatment of IBD.

Abstract: 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.

Abstract: The invention generally relates to polymeric particles suitable for transporting bioactive agents across mucosal barriers. The invention also relates to methods of making and using those polymeric particles.

Abstract: 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.

Abstract: Improved distribution can be achieved by delivering nanoparticles possessing non-adhesive surfaces via CED in a hyperosmolar infusate solution. This delivery strategy minimizes the hindrances imposed by the brain extracellular matrix and reduces the concentration of therapeutic that is confined within perivascular spaces.

Abstract: The invention generally relates to compositions and methods for transporting substances across mucosal barriers. The invention also relates to methods of making and using such substances.

Abstract: Nanocrystals, compositions, and methods that aid particle transport in mucus are provided. In some embodiments, the compositions and methods involve making mucus-penetrating particles (MPP) without any polymeric carriers, or with minimal use of polymeric carriers. The compositions and methods may include, in some embodiments, modifying the surface coatings of particles formed of pharmaceutical agents that have a low water solubility. Such methods and compositions can be used to achieve efficient transport of particles of pharmaceutical agents though mucus barriers in the body for a wide spectrum of applications, including drug delivery, imaging, and diagnostic applications. In certain embodiments, a pharmaceutical composition including such particles is well-suited for administration routes involving the particles passing through a mucosal barrier.

Abstract: Nanocrystals, compositions, and methods that aid particle transport in mucus are provided. In some embodiments, the compositions and methods involve making mucus-penetrating particles (MPP) without any polymeric carriers, or with minimal use of polymeric carriers. The compositions and methods may include, in some embodiments, modifying the surface coatings of particles formed of pharmaceutical agents that have a low water solubility. Such methods and compositions can be used to achieve efficient transport of particles of pharmaceutical agents though mucus barriers in the body for a wide spectrum of applications, including drug delivery, imaging, and diagnostic applications. In certain embodiments, a pharmaceutical composition including such particles is well-suited for administration routes involving the particles passing through a mucosal barrier.

Abstract: 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 nm2, preferably from about 0.5 to about 50 molecules/100 nm2, more preferably from about 0.9 to about 45 molecules/100 nm2.

Abstract: A synthetic gene delivery platform with a dense surface coating of hydrophilic and neutrally charged PEG, capable of rapid diffusion and widespread distribution in brain tissue, and highly effective gene delivery to target cells therein has been developed. Nanoparticles including nucleic acids, are formed of a blend of biocompatible hydrophilic cationic polymers and they hydrophilic cationic polymer conjugated to hydrophilic neutrally charged polymers such as polyethylene glycol. The nanoparticles are coated with polyethylene glycol at a density that imparts a near neutral charge and optimizes rapid diffusion through the brain parenchyma. Methods of treating a disease or disorder of the brain including administering a therapeutically effective amount of nanoparticles densely coated with polyethylene glycol are also provided.

Abstract: Provided are targeted structure-specific particulate-based delivery systems comprising: a nanoparticle; a PEG polymer coating on the surface of the nanoparticle; a targeting moiety conjugated on a surface of the nanoparticle and configured to promote specific binding to a cell surface molecule expressed by a target cell; and a biologically active agent in or on the nanoparticle, wherein the biologically active agent is selected to enhance a desired response in a target cell intracellularly or extracellularly. Methods of treating a disease or disorder administering the delivery system are contemplated.

Abstract: Mucus-penetrating liposomal nanoparticles and methods of making and using thereof are described herein. The nanoparticles contain one or more lipids, one or more PEG-conjugated lipids, and optionally one or more additional materials that physically and/or chemically stabilize the particles. The nanoparticle have an average diameter of about 100 nm to about 300 nm, preferably from about 100 nm to about 250 nm, more preferably from about 100 nm to about 200 nm. The particles are mobile in mucus. The liposomes can further contain one or more therapeutic, prophylactic, and/or diagnostic agent to be delivered to a mucosal surface, such as the CV tract, the colon, the nose, the lungs, and/or the eyes. The liposomes can further contain one or more CEST agents to allow real time imaging of the particles in a live animal. The particles may also further contain an imaging agent, such as a fluorescent label.

Abstract: A synthetic gene delivery platform with a dense surface coating of hydrophilic and neutrally charged PEG, capable of rapid diffusion and widespread distribution in brain tissue, and highly effective gene delivery to target cells therein has been developed. Nanoparticles including nucleic acids, are formed of a blend of biocompatible hydrophilic cationic polymers and they hydrophilic cationic polymer conjugated to hydrophilic neutrally charged polymers such as polyethylene glycol. The nanoparticles are coated with polyethylene glycol at a density that imparts a near neutral charge and optimizes rapid diffusion through the brain parenchyma. Methods of treating a disease or disorder of the brain including administering a therapeutically effective amount of nanoparticles densely coated with polyethylene glycol are also provided.

Abstract: Mucus-penetrating liposomal nanoparticles and methods of making and using thereof are described herein. The nanoparticles contain one or more lipids, one or more PEG-conjugated lipids, and optionally one or more additional materials that physically and/or chemically stabilize the particles. The nanoparticle have an average diameter of about 100 nm to about 300 nm, preferably from about 100 nm to about 250 nm, more preferably from about 100 nm to about 200 nm. The particles are mobile in mucus. The liposomes can further contain one or more therapeutic, prophylactic, and/or diagnostic agent to be delivered to a mucosal surface, such as the CV tract, the colon, the nose, the lungs, and/or the eyes. The liposomes can further contain one or more CEST agents to allow real time imaging of the particles in a live animal. The particles may also further contain an imaging agent, such as a fluorescent label.

Abstract: Methods and materials for treating bacterial vaginosis (“BV”) are provided. Cervicovaginal secretions (“CVS”) from a woman with Lactobacillus crispatus-dominated (>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.

Abstract: 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.

Abstract: Controlled release dosage formulations for the delivery of active agents, especially for treatment of eye diseases or disorders, such as glaucoma, have been developed. These provide release of the active agent, such as ECA or a derivative thereof, for an effective period of time.

Abstract: Methods for increasing the encapsulation or incorporation of Sunitinib into polymeric matrices have been developed. The resulting formulations provide for more sustained controlled release of sunitinib or other inhibitors of JNK signaling, which bind to DLK. Increased loading is achieved using an alkaline solvent system. The pharmaceutical compositions can be administered to treat or reduce neuronal death due to elevated intraocular pressure. Upon administration, the sunitinib or other inhibitor is released over an extended period of time at concentrations which are high enough to produce therapeutic benefit, but low enough to avoid unacceptable levels of cytotoxicity, and which provide much longer release than inhibitor without conjugate.

Abstract: Liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents including therapeutic, prophylactic and diagnostic agents such as the diaCEST MRI contrast agent barbituric acid (BA) were evaluated to determine how to optimize delivery. Polyethylene glycol (PEG)-coated liposomes containing ?7 mol % PEG diffused only approximately 10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol %-PEG liposomes provided improved vaginal distribution compared to 0 and 3 mol %-PEG liposomes.