Yale University

Other

Metcalfe, Susan Marie

Tarek M Fahmy

Eric D Stern

Mark A Reed

William Mark Saltzman

Richard A Flavell

Aleksandar Vacic

Christopher K Breuer

Jason Park

Alyssa Siefert

Stephen H Wrzesinski

Gary L Haller

Lisa D Pfefferle

James Frank Klemic

Joseph Craft

Michael Look

Jung Seok Lee

Peter Fong

Dongin Kim

Michael J Caplan

Ira Mellman

Michael Simons

Pei-Yu Chen

Brian Horsburgh

Albert Sinusas

Daniel Rowe Duncan

Joseph Patterson

Susan Marie Metcalfe

John Martin

Anthony Mathur

Philip Kong

Sean Bickerton

Michael D McHugh

Tarek R Fadel

Alan Dardik

Erin Steenblock

Chris Breuer

Eric Stern

A 'nanolipogel' is a delivery vehicle including one or more lipid layer surrounding a hydrogel core, which may include an absorbent such as a cyclodextrin or ion-exchange resin. Nanolipogels can be constructed so as to incorporate a variety of different chemical entities that can subsequently be released in a controlled fashion. These different incorporated chemical entities can differ dramatically with respect to size and composition. Nanolipogels have been constructed to contain co-encapsulated proteins as well as small hydrophobic drugs within the interior of the lipid bilayer. Agents incorporated within nanolipogels can be released into the milieu in a controlled fashion, for example, nanolipogels provide a means of achieving simultaneous sustained release of agents that differ widely in chemical composition and molecular weight. Additionally, nanolipogels can favorably modulate biodistribution.

Nanolipogel vehicles for controlled delivery of different pharmaceutical agents

Particles with a spatial and/or temporal release profile for delivery of different agents at different times to the same cells of a subject have been developed. The particles include a core polymeric particle containing a polymer and a first agent, a tethering moiety, covalent linker or covalent linkage attached to the core particle, and a tethered particle attached to the particle via the tethering moiety, covalent linker or covalent linkage and containing a second agent, where the agents are released at different times within or to the same cells. The first and second agents may be a therapeutic or prophylactic agent, such as an antigen, an immunomodulator, an anti-neoplastic agent, a hormone, an inhibitor, etc. The particles may form compositions for treating diseases with a spatial and/or temporal treatment regimen.

Particles for spatiotemporal release of agents

It has been discovered that iron-platinum ferromagnetic particles can be dispersed in a polymer and coated into or onto, or directly linked to or embedded on to, medical devices and magnetized. The magnetized devices are used to attract, capture, and/or retain magnetically labeled cells on the surface of the device in vivo. The magnetic particles have an iron/platinum core. Annealing the Fe/Pt particle is very important for introducing a L10 interior crystalline phase. The Fe:Pt molar ratio for creation of the crystal phase is important and a molar range of 1.2-3.0 Fe to Pt (molar precursors, i.e. starting compounds) is desired for magnetization. The magnetic force as a whole can be measured with a 'Super Conducting Quantum Interference Device', which is a sensitive magnetometer. The overall magnetic force is in the range from 0.1 to 2.0 Tesla.

Iron platinum particles for adherence of biologics on medical implants

Multivalent CT or MR contrast agents and methods of making and using thereof are described herein. The agents contain a moiety, such as a polymer, that provides multivalent attachment of CT or MR contrast agents. Examples include, but are not limited to, multivalent linear polymers, branched polymers, or hyperbranched polymers, such as dendrimers, and combinations thereof. The dendrimer is functionalized with one or more high Z-elements, such as iodine. The high Z-elements can be covalently or non-covalently bound to the dendrimer. The dendrimers are confined in order to enhance CT contrast. In some embodiments, the moiety is confined by encapsulating the dendrimers in a material to form particles, such as nanoparticles. In other embodiments, the dendrimer is confined by conjugating the moiety to a material, such as a polymer, which forms a gel upon contact with bodily fluids.

Compositions for nanoconfinement induced contrast enhancement and methods of making and using thereof

Pharmaceutical composition containing poly(bile) acid (PBA) polymers for oral delivery of agent(s) show enhanced uptake by the pancreas, liver, and colon. These nanoparticles show significant retention in the pancreas and colon and are therefore useful for selective delivery. The examples demonstrate efficacy of oral administration of insulin to treat diabetes, and oral induction of tolerance by administration of insulin or ovalbumin in combination with rapamycin. Diabetic animals treated with the insulin or insulin with rapamycin showed normalization of blood glucose levels.

Polymeric bile acid nanocompositions targeting the pancreas and colon

There are provided compositions and methods for treatment of neurodegeneative diseases and CNS injury. The compositions a pharmaceutically acceptable carrier solution; and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a neural stem cell and wherein the nanoparticles further comprise factors such as leukaemia inhibitory factor (LIF); XAV939 and/or one or more of: brain-derived neurotrophic factor (BDNF) or an agonist thereof; epidermal growth factor (EGF) or an agonist thereof; glial cell-derived neurotrophic factor (GDNF) or an agonist thereof; retinoic acid and derivatives thereof; ciliary neurotrophic factor (CTNF) or an agonist thereof; and Wnt5A. The biodegradable nanoparticles may deliver via controlled time release.

Neurotherapeutic nanoparticle compositions comprising leukemia inhibitory factor

Nanoparticulate compositions are disclosed. The nanoparticulate compositions typically include at least one, preferably two or more, active agent(s), one of which is an immunomodulatory compound, loaded into, attached to the surface of and/or enclosed within a delivery vehicle. The delivery vehicles can be nanolipogels including a polymeric core and a lipid shell or a biodegradable polymeric nanoparticle such as a PLGA nanoparticle. Typically, at least one of the active agents is an immunomodulator that increases an immune stimulatory response or decreases an immune suppressive response. In some embodiments, the particle includes both an immunomodulator that increases an immune stimulatory response and an immunomodulator that decreases an immune suppressive response. The particles can be decorated with a targeting moiety that improves delivery to a target cell. Methods of using the compositions to enhance an immune response and treat diseases such as cancer are also disclosed.

Nanoparticulate compositions comprising interferon gamma and losartan for immunotherapy

Compositions and methods for treating or ameliorating the symptoms of inflammatory or autoimmune disease or disorder are described herein. The compositions contain a nanolipogel for sustained delivery of an effective amount of one or more active agents of choice, preferably a drug for treating or ameliorating the symptoms of inflammatory or autoimmune disease or disorder. The nanolipogel includes a lipid bilayer surrounding a hydrogel core, which may optionally include a host molecule, for example, an absorbent such as a cyclodextrin or ion-exchange resin. In preferred embodiments at least one of active agents is an immunosuppressant.

Nanolipogel comprising a polymeric matrix and a lipid shell

The present invention relates to uniform nanostructure biosensors and methods of calibrating the response of nanostructure biosensors. The invention overcomes device to device variability that has made quantitative detection difficult. The described biosensors have uniform characteristics that allow for more reliable comparison across devices. The methods of the invention comprise normalizing the initial current rate, as measured by the nanostructure biosensor following the addition of an analyte, to device characteristics of the biosensor. The device characteristics of the biosensor which can be used to normalize the response include baseline current and transconductance, Calibration of responses allows for the generation of calibration curves for use in all devices to quantitatively detect an analyte, without the need for individual device calibration.

Calibration of nanostructure sensors

Compositions for delivery of growth factors needed for stable Tregs and methods of use thereof are provided. In preferred embodiments, the compositions can induce, increase, or enhance a functionally robust induced CD4 Treg population (e.g., Foxp3+ Treg) in vivo or ex vivo. The compositions generally include delivery vehicles including TGF-&#x3b2; and IL-2. Delivery vehicles include, for example, polymeric particles, silica particles, liposomes, or multilamellar vesicles. The TGF-&#x3b2; and IL-2 are typically co-loaded into, attached to the surface of, and/or enclosed within the delivery vehicle into the same particle for simultaneous co-delivery to cells such as T cells. Preferably the delivery vehicles are targeted to CD4. The compositions and cells treated therewith can be used in various methods of treating, for example, inflammation, inflammatory and autoimmune diseases and disorders, and inducing or maintaining tolerance including graft and transplant tolerance.

Nanoparticle-mediated delivery of cytokines for maintenance of the regulatory T cell phenotype

Carbon nanotube (CNT)-based compositions for activating cellular immune responses are provided. The CNTs function as high surface area scaffolds for the attachment of T cell ligands and/or antigens. The CNT compositions function as artificial antigen-presenting cells (aAPCs) or as modular vaccines. The disclosed CNT aAPCs are efficient at activating T cells and may be used to activate T cells ex vivo or in vivo for adoptive or active immunotherapy.

Carbon nanotube compositions and methods of use thereof

Composite prosthetic patches with covalently bound particles for controlled drug release, and methods of making and using thereof, have been developed. The particles may encapsulate one or more therapeutic, prophylactic or diagnostic agent(s). Generally, the prosthetic patches are decellularized extracellular matrix such as bovine or porcine pericardium or synthetic polymeric materials. The size of the particles ranges from between 1 nm and 1000 &#x3bc;m, preferably from between 10 nm and 500 nm. In some embodiments, the agent is a therapeutic agent for treatment of neointimal hyperplasia. In other embodiments, the agent is a therapeutic agent for suppressing or resolving inflammation. In yet other embodiments, the agent is a therapeutic for mitigating scarring.

Particle conjugated prosthetic patches and methods of making and using thereof

A composition containing a macrophage inhibitor may be administered in an effective amount to prevent, inhibit or reduce restenosis, thrombus or aneurysm formation in implanted polymeric vascular grafts. The composition may be administered prior to vascular graft implantation, at the same time as vascular graft implantation, following vascular graft implantation, or any combination thereof. Examplary macrophage inhibitors include bisphosphonates, anti-folate drugs and antibodies, preferably in a controlled release or liposomal formulation.

Cell-free tissued engineered vascular grafts

Growing community of inventors

New Haven, CT, United States of America

Tarek M Fahmy