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: Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.

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: 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: 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 ˜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 ˜20 mOsm/kg-450 mOsm/kg.

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: Ophthalmic suture materials made from biocompatible and biodegradable polymers with high tensile strength for use in drug delivery, methods of making them, and method of using them for ocular surgery and repair have been developed. The suture materials are made from a combination of a biodegradable, biocompatible polymer and a hydrophilic biocompatible polymer. In a preferred embodiment the suture materials are made from a poly(hydroxyl acid) such as poly(1-lactic acid) and a polyalkylene oxide such as poly(ethylene glycol) or a polyalkylene oxide block copolymer. The sutures entrap (e.g., encapsulate) one or more therapeutic, prophylactic or diagnostic agents and provide prolonged release over a period of at least a week, preferably a month.

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 nano particles densely coated with polyethylene glycol are also provided.

Abstract: A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.

Abstract: The present invention generally relates to reducing the mucoadhesive properties of a particle. In some embodiments, the particle is coated with and/or associated with a (poly(ethylene glycol))-(poly(propylene oxide))-(poly(ethylene glycol)) triblock copolymer. Methods for preparing inventive particles using a poly(ethylene glycol)-vitamin E conjugate as a surfactant are also provided. In some embodiments, methods are provided comprising administering to a subject a composition of particles of the present invention. Such particles with reduced mucoadhesive properties are useful in delivering agents to mucosal tissues such as oral, ophthalmic, gastrointestinal, nasal, respiratory, and genital mucosal tissues.

Abstract: Ophthalmic suture materials made from biocompatible and biodegradable polymers with high tensile strength for use in drug delivery, methods of making them, and method of using them for ocular surgery and repair have been developed. The suture materials are made from a combination of a biodegradable, biocompatible polymer and a hydrophilic biocompatible polymer. In a preferred embodiment the suture materials are made from a poly(hydroxyl acid) such as poly(l-lactic acid) and a polyalkylene oxide such as poly(ethylene glycol) or a polyalkylene oxide block copolymer. The sutures entrap (e.g., encapsulate) one or more therapeutic, prophylactic or diagnostic agents and provide prolonged release over a period of at least a week, preferably a month.

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: 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 ˜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 ˜20 mOsm/kg-450 mOsm/kg.

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: 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 of lactobacillus typically found in the human vagina, e.g. Lactobacillus crispatus, L. iners, L. gasseri, L jensenii, 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: 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 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 ˜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 ˜20 mOsm/kg-450 mOsm/kg.

Abstract: Surface conjugated diamagnetic Chemical Exchange Saturation Transfer (diaCEST) agent carriers and methods of making and using are described herein. The particles are safe alternatives to conventional paramagnetic or superparamagnetic metal-based MRI contrast agents that are often toxic and therefore not biocompatible. The carriers described herein can provide simultaneous monitoring of multiple particle types labeled with ‘multicolor’ diaCEST contrast agents. In some embodiments, the carriers are micro- and/or nanoparticles. In other embodiments, the carriers are liposomes. In some embodiments, the particles and/or liposomes are mucus penetrating. In other embodiments, the particles and/or liposomes are not mucus penetrating.

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.