Two-stage microparticle-based therapeutic delivery system and method
Inventors
Goldberg, Manijeh Nazari • Manzi, Aaron • LaPorte, Brandon • Birdi, Amritpreet
Assignees
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Publication Number
US-11617722-B2
Publication Date
2023-04-04
Expiration Date
Abstract
A system for delivery of a therapeutic agent to a site in mucosal tissue is provided. The system includes a porous, mucoadhesive polymeric matrix having a first and a second opposed surfaces. The matrix is formed by a composition including chitosan. The composition may also include any or all of a hydration promotor, a microparticle adhesion inhibitor, and a microparticle aggregation inhibitor. A plurality of microparticles having an average diameter between 500 nm and 2000 nm are embedded within the matrix. The microparticles contain a therapeutic agent and have a coating around the therapeutic agent. The first surface of the matrix is configured to be attached to the site in the mucosal tissue and the matrix is configured to provide controlled release of the microparticles through the first surface. The coating of the microparticles includes chitosan so as to provide controlled release of the agent from the microparticles.
Core Innovation
The invention provides a system for delivery of a therapeutic agent to a site in mucosal tissue using a polymeric matrix comprising chitosan, a hydration promoter, a microparticle adhesion inhibitor, and a microparticle aggregation inhibitor. The polymeric matrix has first and second opposed surfaces, and the microparticles are embedded within the matrix so that the microparticles are directly surrounded by, and in contact with, the matrix. The microparticles comprise the therapeutic agent and chitosan and have an average diameter between 500 nm and 2000 nm, and the hydration promoter, the adhesion inhibitor, and the aggregation inhibitor are compounds mutually distinct from one another.
The first surface of the matrix is configured to be attached to the site in the mucosal tissue and the matrix is configured to provide controlled release of the microparticles through the first surface. The microparticle adhesion inhibitor comprises hydroxypropylmethylcellulose (HPMC), and the microparticle aggregation inhibitor is present in a concentration of 0.1% to 50% by weight. The second opposed surface is configured to be water-permeable in some configurations.
The invention also includes a manufacturing method in which microparticles comprising a therapeutic agent and chitosan are formed with an average diameter between 500 nm and 2000 nm, then a second mixture comprising the first mixture, chitosan, a hydration promoter, a microparticle adhesion inhibitor, and a microparticle aggregation inhibitor is formed. The second mixture is frozen to form a frozen layer precursor, and the frozen layer precursor is dried to form a polymeric matrix with the microparticles embedded. In some embodiments, multi-layer devices are formed by applying a second layer precursor to the frozen layer precursor to form a solid having a first layer and a second layer.
Claims Coverage
The document contains two independent claims covering a mucosal-tissue delivery system and a manufacturing method for such a delivery system, with multiple dependent refinements that further define component identities, functional surface properties, quantitative composition constraints, and optional multi-layer formation. The main inventive features are centered on a chitosan-containing polymeric matrix with distinct hydration, adhesion, and aggregation inhibitors, and embedded therapeutic-agent/chitosan microparticles sized between 500 nm and 2000 nm.
Chitosan polymeric matrix with mutually distinct hydration, adhesion, and aggregation inhibitors
A polymeric matrix with first and second opposed surfaces comprising chitosan, a hydration promoter, a microparticle adhesion inhibitor comprising hydroxypropylmethylcellulose (HPMC), and a microparticle aggregation inhibitor in a concentration of 0.1% to 50% by weight, wherein the hydration promoter, the microparticle adhesion inhibitor, and the microparticle aggregation inhibitor are compounds mutually distinct from one another.
Embedded therapeutic-agent and chitosan microparticles sized 500 nm to 2000 nm
A plurality of microparticles having an average diameter between 500 nm and 2000 nm, wherein the microparticles are embedded within the matrix so as to be directly surrounded by, and in contact with, the matrix, and the microparticles comprise a therapeutic agent and chitosan.
First-surface attachment to mucosal tissue with controlled release through the first surface
The first surface of the matrix is configured to be attached to the site in the mucosal tissue and the matrix is configured to provide controlled release of the microparticles, through the first surface.
Manufacturing by freezing and drying a chitosan second mixture containing embedded microparticles
Forming a first mixture comprising a plurality of microparticles having an average diameter between 500 nm and 2000 nm, wherein the microparticles comprise a therapeutic agent and chitosan; forming a second mixture comprising the first mixture, chitosan, a hydration promoter, a microparticle adhesion inhibitor, and a microparticle aggregation inhibitor; freezing the second mixture to form a frozen layer precursor; and drying the frozen layer precursor to form a polymeric matrix with the microparticles embedded within the matrix.
Multi-layer formation by applying a second layer precursor to a frozen layer precursor
Applying a second layer precursor to a frozen layer precursor to form a solid having a first layer and a second layer.
Overall, claim coverage focuses on a chitosan-containing polymeric matrix with separate hydration-promoter, adhesion-inhibitor, and aggregation-inhibitor compounds and embedded therapeutic-agent/chitosan microparticles sized 500 nm to 2000 nm, with controlled release through a first surface configured for attachment to mucosal tissue. The independent method claim covers forming microparticles, incorporating them into a chitosan second mixture containing the same classes of inhibitor and promoter, then freezing and drying to yield an embedded-microparticle polymeric matrix, with optional multi-layer formation by applying a second layer precursor.
Stated Advantages
Controlled release of the microparticles through the first surface configured to be attached to the site in the mucosal tissue.
Documented Applications
Delivery of a therapeutic agent to a site in mucosal tissue.
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