Protein-loaded PLGA nanospheres
Inventors
Lindsey, Brock A • MARKEL, Justin E • LACINSKI, Ryan A • NOORE, Jabeen
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Assignees
MemberWest Virginia UniversityWest Virginia UniversityWest Virginia University is a public R1 research institution offering diverse undergraduate and graduate programs across science, engineering, business, creative arts, and media. The university emphasizes experiential learning, research, and innovation, with notable strengths in academic program development, research excellence, community engagement, and a commitment to affordability, career readiness, and student success. WVU supports a vibrant campus environment, industry partnerships, and impactful scholarship, preparing students for careers through hands-on education, research, and applied learning.
West Virginia University is a public R1 research institution offering diverse undergraduate and graduate programs across science, engineering, business, creative arts, and media. The university emphasizes experiential learning, research, and innovation, with notable strengths in academic program development, research excellence, community engagement, and a commitment to affordability, career readiness, and student success. WVU supports a vibrant campus environment, industry partnerships, and impactful scholarship, preparing students for careers through hands-on education, research, and applied learning.
Publication Number
US-12214046-B2
Publication Date
2025-02-04
Expiration Date
Abstract
The present disclosure provides compositions comprising protein encapsulated nanoparticles, and methods of making said compositions. In an aspect, a composition may comprise a drug delivery vector and a therapeutic substance, wherein the composition elutes at least 1.0 pg of the therapeutic substance per 100,000 particles of the drug delivery vector over a period of time under conditions of a drug delivery vector release buffer, wherein the therapeutic substance, drug delivery vector and drug delivery vector release buffer comprise a solution, wherein the solution is centrifuged and a portion stored at about 1 to 10° C., and wherein the elution of the therapeutic substance is determined by ELISA assay. This disclosure further describes a method of controlling an immunophenotype in a patient suffering from a disease which impacts the immune system.
Core Innovation
The invention relates to PLGA nanospheres prepared by forming a first emulsion comprising PLGA having from 50% to 90% lactide, a sorbitan fatty acid ester, an organic solvent, and a first aqueous phase comprising IL-12 and a species-specific whole serum, a species-specific engineered serum albumin, or a species-specific native serum albumin. A second emulsion is then formed comprising the first emulsion and a second aqueous phase comprising polyvinyl alcohol (PVA) and a polyoxyethylene sorbitan fatty acid ester.
The process further includes evaporating the organic solvent from the second emulsion to form the PLGA nanosphere. The disclosed formulation is protein-loaded, including IL-12, and is described as providing controlled, biphasic elution over extended periods. Protein bioactivity is maintained as assessed by ELISA-based bioactive release, including IL-12 release.
The disclosure additionally provides systemic biodistribution data and links sustained IL-12 delivery to immunophenotype modulation. Immunophenotyping is used to monitor immune cell subsets and immunological cytokine-related effects, including modulation of T cell exhaustion markers and changes involving PMN-MDSCs and NK cells, in murine osteosarcoma models. Database-driven selection and adjustment of immunomodulating treatment protocols is described in connection with these outcomes.
Claims Coverage
The relevant portion includes one independent claim, covering preparation of a specific PLGA nanosphere via a double-emulsion route with defined IL-12 and species-specific serum/albumin components, plus dependent claim refinements that narrow surfactant identity, serum/albumin type, and PLGA lactide fraction, and optionally add a pharmaceutically acceptable excipient.
Double-emulsion PLGA nanosphere with IL-12 and species-specific serum/albumin
Forming a first emulsion comprising PLGA having from 50% to 90% lactide, a sorbitan fatty acid ester, an organic solvent, and a first aqueous phase comprising IL-12 and a species-specific whole serum, a species-specific engineered serum albumin, or a species-specific native serum albumin; forming a second emulsion comprising the first emulsion and a second aqueous phase comprising PVA and a polyoxyethylene sorbitan fatty acid ester; evaporating the organic solvent from the second emulsion to form the PLGA nanosphere.
Nanosphere with specific polyoxyethylene sorbitan monooleate and sorbitan monostearate components
The PLGA nanosphere wherein the polyoxyethylene sorbitan fatty acid ester includes polyoxyethylene sorbitan monooleate and the sorbitan fatty acid ester includes sorbitan monostearate.
Nanosphere using species-specific native serum albumin in the first emulsion
The PLGA nanosphere wherein the first emulsion contains species-specific native serum albumin.
Nanosphere using PLGA comprising 50% to 75% lactide
The PLGA nanosphere wherein the PLGA comprises from 50% to 75% lactide.
Nanosphere using PLGA comprising 50% lactide
The PLGA nanosphere wherein the PLGA comprises 50% lactide.
Dosage form including the PLGA nanosphere and a pharmaceutically acceptable excipient
A dosage form comprising the PLGA nanosphere together with a pharmaceutically acceptable excipient.
Overall claim coverage centers on a double-emulsion PLGA nanosphere preparation route with IL-12 plus a species-specific serum/albumin component, further refined by specific ester/surfactant selection, selection among whole serum versus engineered or native serum albumin, constrained PLGA lactide fractions, and optionally incorporation into a dosage form with a pharmaceutically acceptable excipient.
Stated Advantages
Controlled, biphasic elution over extended periods.
Bioactive protein release of IL-12, assessed by ELISA-based measurements.
Documented Applications
Sustained IL-12 delivery associated with immunophenotype modulation using immunophenotyping and monitoring of immune cell subsets in murine osteosarcoma models.
Database-driven selection and adjustment of immunomodulating treatment protocols in connection with immunophenotype outcomes in the described models.
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