University of Pittsburgh

Massachusetts Institute of Technology

Ri.med Foundation

Svstem of Higher Education 1Tts

Steven R Little

Riccardo Lucca Gottardi

Morgan V Fedorchak

Joel Steven Schuman

Andrew Jason Glowacki

Abhinav Prakash Acharya

Siddharth Jhunjhunwala

Mintai Peter Hwang

Daniel DeSantis

Peter Alexander

Angus W Thomson

Michelle L Guaragno

Giorgio Raimondi

Anthony Cugini

Michelle L Ratay

Patrick A Bianconi

Stephen C Balmert

Robert Samuel Langer

Daniel Griffith Anderson

David M Lynn

David A Vorp

Justin Sol Weinbaum

Tatum Varut Tarin

Kaladhar Kamalasanan

Sam N Rothstein

Katherine Lorentz

Jeffrey Krawiec

Morgan Virginia Fedorchak

Morgan V DiLeo

The absence of regulatory T cells (Treg) may underlie disorders including but not limited to autoimmunity, dermatitis, periodontitis and even transplant rejection. Enhancing local numbers of Treg through in situ Treg expansion or induction is contemplated herein as a treatment option for these disorders. Current methods for in vivo Treg expansion are not Treg specific and are associated with many adverse side-effects. The data presented herein provides in vitro testing of a Treg-inducing microparticle providing a predictable controlled release for combinations of cytokines and drugs (e.g., IL-2, TGF-β, and/or rapamycin) resulting in targeted Treg migration. These controlled release microparticles are also capable of inducing FoxP3+ Treg in human cells in vitro suggesting that these compositions be developed into an in vivo Treg induction and expansion therapy.

Controlled release formulations for the induction and proliferation of blood cells

A method for sustained delivery of an agent to an ocular organ in a subject, comprising topically delivering to the ocular surface a liquid thermoresponsive hydrogel comprising agent-loaded polymer microparticles, wherein the agent is sustainably released for a period of at least five days.

Thermoresponsive hydrogel containing polymer microparticles for noninvasive ocular drug delivery

Controlled release of VIP from PLGA microparticles was accomplished and varied through use of different polymer molecular sizes, addition of solutes to the inner aqueous phase, and use of our computer model. Released VIP from microparticles appeared to be bioactive and caused DCs to produce more CCL22 than DCs treated with blank particles at 7 and 24 hours. Additionally, DCs treated with VIP microparticle releasates recruited higher percentages of FoxP3+ T-cells in in vitro chemotaxis studies. Testing in a mouse model in vivo indicated that VIP microparticles have significant therapeutic potential to treat periodontal disease by reducing the bone loss in infected mice relative to the blank group.

Vasoactive intestinal peptide release from microparticles

Methods for treating an ear condition in a subject, comprising topically administering to the ear of the subject in need thereof a composition comprising: (i) an anti-infective agent-loaded biodegradable polymer microspheres; and (ii) a thermoresponsive hydrogel.

Thermoresponsive hydrogel containing polymer microparticles for controlled drug delivery

The present invention provides microparticles that induce the migration of multipotent stem cells to the anatomical site of the microparticles. Various release profiles are demonstrated that depend upon the relative concentration of alginate in the chemokine-loaded microparticle. Local administration and/or intraarticular injection of the microparticles are useful in conditions such as osteoarthritis. Targeted systemic delivery of the alginate chemokine microparticles to distant anatomical sites subjected to autoimmune disease symptomology can be performed by encapsulation within liposomes having targeting ligands. Consequently, upon the creation of the appropriate chemokine gradient, multipotent stem cells will migrate to the distant anatomical site where the liposomes are attached.

Autoimmune disease treatment with chemokine-loaded alginate microparticles

A method for treating an ocular disorder in a subject comprising administering a therapeutic agent-loaded carrier to an ocular site of the subject in need thereof, wherein the therapeutic agent loaded-carrier provides controlled delivery of the therapeutic agent under conditions suitable for recruiting regulatory T cells to an ocular region of interest or inducing regulatory T cells in an ocular region of interest.

Biomimetic drug delivery of an immunomodulatory agent for the treatment of ocular conditions

The present disclosure relates to probiotics and probiotic compositions having modified energy metabolisms (e.g., modifying, metabolizing, or storing energy molecules, e.g., lipids, before the energy molecules are absorbed by a host subject), and thus modulating the absorption of the energy molecules by the host subject. The present disclosure also relates to methods of making such probiotics and probiotic compositions. The present disclosure further relates to methods of regulating (e.g., maintaining or reducing) body weight in a subject (e.g., a subject having a healthy BMI, a subject having an overweight BMI, a subject having an obese BMI), using the probiotics and probiotic compositions disclosed herein.

Probiotics and probiotic compositions for regulating body weight

A method for treating an ocular disorder in a subject comprising administering a therapeutic agent-loaded carrier to an ocular site of the subject in need thereof, wherein the therapeutic agent is a histone deactylase inhibitor.

Treatment of ocular conditions utilizing a histone/protein deacetylase inhibitor

Provided herein is a drug delivery device and composition, such as a particle, comprising conditioned medium. Also provided herein is a method of preparing polymeric particles for release of conditioned medium. Further, a tissue growth scaffold comprising particles for release of conditioned medium is provided.

Artificial cells and delivery devices for use in tissue engineering, and related methods

A method for making a modified release composition, comprising:

Engineered microparticles for macromolecule delivery

Thermoresponsive hydrogel containing polymer microparticles for controlled drug delivery to the ear

The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Tcells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Tcell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Artificial cell constructs for cellular manipulation

Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.

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Allison Park, PA, United States of America

Steven R Little