Aggregating microparticles for medical therapy
Inventors
Yu, Yun • Kays, Joshua • Yang, Ming • Cleland, Jeffrey L.
Assignees
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Publication Number
US-11331276-B2
Publication Date
2022-05-17
Expiration Date
Abstract
The present invention is a surface treated drug-loaded solid (e.g., non-porous) microparticle that aggregates in vivo to form a consolidated larger particle for medical therapy. In one embodiment, the particles are used for ocular therapy. Processes for producing the surface treated microparticle and injectable formulations which include the surface treated microparticle are also provided. When used in the eye, long-term consistent intraocular delivery can be achieved without disrupting vision and minimizing undesirable inflammatory responses.
Core Innovation
The invention relates to surface-modified aggregating microparticles for ocular therapy. A method for the treatment of an ocular disorder is provided by administering surface-modified aggregating microparticles that are injected into the eye and aggregate in vivo to form at least one pellet for sustained drug delivery.
The microparticles comprise poly(lactide-co-glycolide) covalently linked to polyethylene glycol and a therapeutic agent encapsulated in biodegradable microparticles. The microparticles contain surfactant in a specified range and are surface-modified to contain less surfactant than a microparticle prior to the surface modification.
The microparticles have a mean diameter between 10 μm and 60 μm, and the surface modification is performed at a temperature less than about 18° C. The disclosed platform provides sustained intravitreal drug levels while reducing dispersion, burst release, and inflammation.
Claims Coverage
The document includes one independent method claim directed to treating an ocular disorder using surface-modified aggregating microparticles that are injected into the eye, aggregate in vivo to form at least one pellet, and provide sustained drug delivery for at least one month. The inventive features include pellet-forming in vivo aggregation, PLGA covalently linked to PEG with encapsulated therapeutic agent, defined microparticle size and surfactant content, and low-temperature surface modification to reduce surfactant.
In vivo aggregation into sustained pellets
Administering surface-modified aggregating microparticles injected into the eye that aggregate in vivo to form at least one pellet to provide sustained drug delivery for at least one month, including pellets of at least 500 μm.
PLGA covalently linked to PEG with encapsulated therapeutic agent
The microparticles comprise poly(lactide-co-glycolide) covalently linked to polyethylene glycol, surfactant, and an effective amount of the therapeutic agent encapsulated in the biodegradable microparticle.
Defined microparticle mean diameter range
The surface-modified aggregating microparticles have a mean diameter between 10 μm and 60 μm.
Reduced surfactant via low-temperature surface modification
The microparticles contain from about 0.001 percent to about 1 percent surfactant, are surface-modified to contain less surfactant than a microparticle prior to the surface modification, and the surface is modified at a temperature less than about 18° C.
Overall, the claim coverage centers on a method that uses injected surface-modified aggregating microparticles which aggregate in vivo into at least one pellet for sustained ocular drug delivery for at least one month, with microparticles formed from PLGA covalently linked to PEG and containing an encapsulated therapeutic agent. The claim further limits particle size and requires surfactant content reduction achieved by low-temperature surface modification.
Stated Advantages
Sustained drug delivery for at least one month.
Reduction of surfactant compared to a microparticle prior to surface modification.
Aggregation in vivo in the eye to form at least one pellet.
Reduces burst release and inflammation.
Minimizes vision disruption by forming consolidated pellets outside the visual axis.
Documented Applications
Treatment of an ocular disorder by administering surface-modified aggregating microparticles injected into the eye for sustained drug delivery.
In vivo ocular delivery including intravitreal injection with sustained drug levels in vitreous and ocular compartments.
Wet age-related macular degeneration is specified as an ocular disorder in a dependent claim.
Delivery of therapeutically effective amounts of therapeutic agents selected from dorzolamide, brinzolamide, brimonidine, and timolol is specified in dependent claims.
Delivery of sunitinib, including sunitinib malate, is described as an example therapeutic agent context.
Delivery of sunitinib malate as the therapeutic agent is specified in a dependent claim.
Delivery by intravitreal injection is specified in a dependent claim.
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