The Johns Hopkins University

Massachusetts Institute of Technology

The Penn State Research Foundation

Other

Kala Pharmaceuticals, Inc.

University System of Maryland

Spiral Therapeutics, Inc.

The Penn Research Foundation

Justin Scot Hanes

Laura M Ensign

Robert Samuel Langer

David A Edwards

Samuel K Lai

Jeffrey S Hrkach

Noah Lotan

Tao Yu

Ming Yang

Giovanni Caponetti

Jie Fu

Elizabeth M Enlow

Alexey Popov

Hongming Chen

James Bourassa

Richard A Cone

Colin R Gardner

Abdellaziz Ben-Jebria

Jung Soo Suk

Peter John McDonnell

Katharina Maisel

Peter Anthony Campochiaro

Panagiotis Mastorakos

Ashley Behrens

Renata T Kashiwabuchi

Yasin A Khan

Graeme F Woodworth

Qingguo Xu

Abdell Aziz Ben-Jebria

Michael T McMahon

Clark Zhang

Edward Fuchs

Craig W Hendrix

Hai-Quan Mao

Donald Jeffrey Zack

Zhiyong Yang

Cynthia Ann Berlinicke

Derek Stuart Welsbie

Kannie Wai Yan Chan

Shuming Zhang

Giovannia Caponetti

Fabiana Kimie Kashiwabuchi

Carmen Evora

Kunal S Parikh

Olcay Mert

Barbara S Slusher

Jin Yang

Jeffrey L Cleland

Hugo Peris

Andrew Ayoob

Jeffrey A Winkles

Denis Wirtz

Anthony J Kim

Nikita Oskolkov

Anne Le

Walter J Stark

Bing Wang

Xinglu Huang

Craig S Schneider

Himat Patel

Himatkumar Patel

Kannie M Y Chan

Jennifer Fiegel

Elizabeth A Nance

Qing Pan

Nicholas J Boylan

Eric Mark Krauland

Michelle Rose Dawson

Lixia Luo

Carmen Herrero

Graeme Woodworth

Kannie Wai Chan

Nicholas Boylan

Yun Yu

Joshua Kays

Michael T Mcmahon

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.

Nanocrystals, compositions, and methods that aid particle transport in mucus

Compositions and methods for treating eye disorders by administering a drug delivery system into an eye compartment of the patient, wherein the drug delivery system contains a particle containing a core; a coating associated with the particle, wherein the coating is covalently or non-covalently associated with the particle and presents a hydrophilic region to the environment around the particle; and a therapeutic agent are disclosed. The eye compartment can exhibit reduced inflammation or TOP after administration of the drug delivery systems to a patient than if a drug delivery system including an uncoated particle were administered to the patient.

Sustained delivery of therapeutic agents to an eye compartment

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

Non-linear multiblock copolymer-drug conjugates for the treatment and prevention of diseases and disorders of the eye are provided. The polymer-drug conjugates can form nanoparticles, microparticles, and implants that are capable of effectively delivering therapeutic levels of one or more active agents for an extended period of time. Administration to the eye of an active agent in the form of a non-linear multiblock copolymer-drug conjugate produces decreased side effects when compared to administration of the active agent alone. Also provided are methods of treating intraocular neovascular diseases, such as wet age-related macular degeneration as well as diseases and disorders of the eye associated with inflammation, such as uveitis.

Non-linear multiblock copolymer-drug conjugates for the delivery of active agents

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

A protein nanocage formulation with enhanced mucus penetration capability and colloidal stability provides controlled delivery of therapeutic, prophylactic, or diagnostic agents to tumors. A dense coating of a surface altering agent such as polyethylene glycol on self-assembled protein nanocages enhances the rapid and uniform distribution of the formulation at mucosal tissues following topical administration, enhances circulation time following intravenous administration, and enhances penetration into hypoxic tumor cores. The density and the molecular weight of surface altering agents are selected to allow the protein nanocages to also bind to tumor cell receptors and release chemotherapeutic agents after tumor cell uptake. Agents delivered in the formulation have better efficacy compared to carrier-free agents. A method of making the protein nanocage formulation with enhanced mucus penetration and colloidal stability is also provided.

Protein nanocages with enhanced mucus penetration for targeted tissue and intracellular delivery

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.

Targeted structure-specific particulate delivery systems

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.

Sunitinib formulations and methods for use thereof in treatment of glaucoma

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.

Highly stable biodegradable gene vector platforms for overcoming biological barriers

A system for forming twisted or aligned electrospun fibers has been developed. The collector for the electrospun fibers is capable of rotation. In some instances, fibers are formed between two collectors, at least one of which rotates to twist the fibers into a multifilament bundle with increased strength. In a second embodiment, a cylindrical collector rotates, and charged polymer jet uniformly coats the surface of the collector. When a drum collector rotates at a high speed, electrospun fibers align and form an array. Optionally, different active agents can be included in the electrospinning solutions to form fiber constructs with different strengths and controlled release profiles, providing a reproducible method to generate complexed structures based on electrospun fibers and controlled drug delivery profiles.

Process for making aligned or twisted electrospun fibers

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Baltimore, MD, United States of America

Justin Scot Hanes