Polymeric nanoparticle compositions for encapsulation and sustained release of protein therapeutics
Inventors
Mao, Hai-quan • Reddy, Sashank • Ke, Xiyu • Qiu, Chenhu • Lucena Comingues, Daniel • Howard, Gregory P.
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Assignees
MemberJohns Hopkins UniversityJohns Hopkins UniversityFounded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Founded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Publication Number
US-12648916-B2
Publication Date
2026-06-09
Expiration Date
Abstract
Described are new biodegradable nanoparticle platforms for encapsulation and sustained release of protein therapeutics through a scalable and reproducible method. Specifically nanoparticles comprising a complex comprising a protein, or peptide, and a counter ion polymer are described.
Core Innovation
This disclosure describes biodegradable polymeric nanoparticle platforms for encapsulating protein therapeutics using polyelectrolyte complexes (PECs). The PEC is formed between a pharmaceutical agent and a counter ion polymer having an opposite electrostatic charge that enables electrostatic binding between the counter ion polymer and the pharmaceutical agent. The counter ion polymer is selected from dextran sulfate (DS), heparin, heparin sulfate, hyaluronic acid, or a combination thereof, and the PEC is configured to be uniformly distributed throughout a hydrophobic biodegradable polymer core.
The invention provides flash-based fabrication approaches aimed at producing nanoparticles with the pharmaceutical agent distributed within the polymer architecture. One approach uses two-step flash nanocomplexation (FNC) followed by flash nanoprecipitation (FNP) to co-precipitate PEG-b-PLLA or PEG-b-PCL with PECs. The other approach uses a single-step process in which PEC formation and solvent-induced phase separation occur simultaneously in a flash mixing device (CIJ/MIVM), producing monolithic nanoparticles with the protein distributed throughout the polymer matrix or micelles for PEG-co-polyester blocks.
The disclosed nanoparticles are characterized and designed for controllable, sustained protein release behavior. The release profile is described as having a biphasic burst followed by near zero-order release over approximately 2 weeks to months. The platform is described as providing tunable nanoparticle size, a polydispersity index of ≤ 0.3, and protein loading in the range of about 2–25% w/w, with reported encapsulation efficiencies roughly in the range of 60–99% depending on formulation.
Claims Coverage
Independent claim clm-00001 provides coverage for nanoparticles comprising a hydrophobic biodegradable polymer core and a uniformly distributed polyelectrolyte complex of a pharmaceutical agent and a counter ion polymer with opposite electrostatic charge. The coverage includes three inventive features governing core composition, electrostatic binding, and counter ion polymer selection.
Hydrophobic biodegradable polymer core with uniformly distributed polyelectrolyte complex
A nanoparticle comprising a hydrophobic biodegradable polymer core; and a polyelectrolyte complex comprising a pharmaceutical agent and a counter ion polymer, wherein the polyelectrolyte complex is uniformly distributed throughout the hydrophobic biodegradable polymer core.
Opposite electrostatic charge enabling electrostatic binding between pharmaceutical agent and counter ion polymer
A polyelectrolyte complex in which the counter ion polymer has an opposite electrostatic charge enabling it to bind electrostatically to the pharmaceutical agent.
Counter ion polymer selection from specified oppositely charged polymers
The counter ion polymer is selected from the group comprising dextran sulfate (DS), heparin, heparin sulfate, hyaluronic acid, or a combination thereof.
Across the independent claim, the main inventive coverage is directed to nanoparticles with a hydrophobic biodegradable polymer core containing a uniformly distributed polyelectrolyte complex of a pharmaceutical agent and a counter ion polymer, where binding is enabled by opposite electrostatic charge and the counter ion polymer is limited to DS, heparin/heparin sulfate, hyaluronic acid, or combinations.
Stated Advantages
Controllable, sustained protein release behavior including a biphasic burst followed by near zero-order release over approximately 2 weeks to months.
Tunable nanoparticle size of about 30–1000 nm with polydispersity index (PDI) of ≤ 0.3.
Protein loading in the range of about 2–25% w/w.
Encapsulation efficiency roughly in the range of 60–99% depending on formulation.
Documented Applications
Encapsulation and in vitro release testing using model proteins including lysozyme, ovalbumin, and IgG.
Interested in licensing this patent?