Autoimmune disease treatment with chemokine-loaded alginate microparticles

Inventors

Little, Steven R. • Gottardi, Riccardo • Hwang, Mintai Peter • DeSantis, Daniel

Assignees

RiMed Foundation • University of Pittsburgh

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Publication Number

US-12178849-B2

Patent

Publication Date

2024-12-31

Expiration Date


Abstract

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.

Core Innovation

The invention relates to controlled release microparticles that include a chemokine, alginate, and hypromellose (HPMC). The alginate is present at a concentration from about 1% to about 4% v of alginate/v of the microparticle, and the controlled release is designed to provide chemokine release kinetics over an extended period.

The microparticles are used to create a biomimetic chemokine gradient, and the chemokine release profile is described as being tuned to control phase timing during release. The gradient is proposed to induce migration of multipotent stem cells, including mesenchymal stem cells (MSCs), to anatomical sites.

In some embodiments described, the microparticles are incorporated into a targeted systemic delivery architecture in which liposomes carry targeting ligands. The supporting context describes validation and evaluation of microparticle characteristics and MSC migration, including microparticle erosion and cytotoxicity assessment, and in vivo and in vitro migration and joint injury models.

Claims Coverage

The document provides two independent claims. The inventive features center on the specific combination of chemokine with alginate at about 1% to about 4% v/v and hypromellose (HPMC), and on administering the microparticle to achieve chemokine release that forms a biomimetic gradient.

Controlled release microparticle composition with chemokine, alginate (1% to 4% v/v), and HPMC

A controlled release microparticle comprising a chemokine, alginate at a concentration from about 1% to about 4% v of alginate/v of the microparticle, and hypromellose (HPMC).

Method of treating an autoimmune disease using the controlled release microparticle

A method of treating an autoimmune disease in a subject in need thereof, comprising administering a controlled release microparticle comprising a chemokine, alginate at a concentration from about 1% to about 4% v of alginate/v of the microparticle, and hypromellose (HPMC).

Claim coverage focuses on the disclosed controlled release microparticle framework and its use in treating autoimmune disease by administering the microparticle to form a biomimetic chemokine gradient.

Stated Advantages

Documented Applications

No documented applications found

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