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Efficient Encapsulation of Hydrophilic Biologics into Nanocarriers

详细技术说明
Efficient Encapsulation of Hydrophilic Biologics into NanocarriersPrinceton Docket # 18-3414-1 The research team at Princeton University has demonstrated a novel and efficient method to encapsulate highly water-soluble biologic active pharmaceutical ingredients into nanocarriers using a single precipitation step. Nanoprecipitation of active pharmaceutical ingredients into drug carriers is an attractive method for producing formulations with improved nanoparticle stability and biological efficacies. However, nanoprecipitation techniques are generally applicable for only highly hydrophobic and water-insoluble active pharmaceutical ingredients. Currently, water-soluble biologics are typically encapsulated through water-in-oil-in-water emulsions or liposomal processes that require multi steps, suffer from poor encapsulation efficiencies, or exhibit low drug mass loadings. The team at Princeton University has demonstrated a new approach that enables formation of nanoparticles from previously intractable compounds. As a proof of concept, highly hydrophilic active pharmaceutical ingredients including gentamicin (LogP=-4.21) and polymyxin B (Log P=-5.6) were encapsulated. For polymyxin B, nanocarriers of 100-200 nm in size displaying release rates over 3 days were produced. Nanocarrier properties, including stability and release rates, can be tuned using this process. Further, the nanoparticle are assembled via flash nanoprecipitation (FNP) process, which is a continuous process that is similar to currently existing industrial processes, has been shown to be compatible for other formulations, and is currently being scaled up to an industrially relevant production size and rate. Application- Controlled release formulation for hydrophilic biologics  Advantages - Encapsulation of poly peptides, proteins, and water soluble drugs into nanocarriers - Efficient single step process via precipitation - Nanocarrier properties (stability, release rates, etc.) are tunable - Economical, scalable, and continuous process (flash nanoprecipitation) PublicationLu et al. Hydrophobic Ion Pairing of Peptide Antibiotics for Processing into Controlled Release Nanocarrier Formulations. Molecular Pharmaceuticals, 2018, 15, 216-225. doi: 10.1021/acs.molpharmaceut.7b00824. Intellectual Property & Development StatusProof of concept was demonstrated with highly hydrophilic active pharmaceutical ingredients including gentamicin (LogP = -4.21) and polymyxin B (Log P = -5.6) were encapsulated. For polymyxin B, nanocarriers of 100-200 nm in size displaying release rates over 3 days were produced. Nanocarrier properties, including stability and release rates, can be tuned using this process. Patent protection is pending. Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.  The Inventors Robert K. Prud’homme is a Professor of Chemical and Biological Engineering and the Director of the Program in Engineering Biology at Princeton University. His research focuses on how weak forces at the molecular level determine macroscopic properties at larger length scales. Equal time is spent understanding the details of molecular-level interactions using NMR, neutron scattering, x-ray scattering, or electron microscopy and making measurements of bulk properties such as rheology, diffusion of proteins in gels, drop sizes of sprays, or pressure drop measurements in porous media. A major focus of his lab’s research is on using self-assembly to construct nanoparticles for drug delivery and imaging. His work is highly interdisciplinary; many of the projects involve joint advisors and collaborations with researchers at NIH, Argonne National Labs, CNRS in France, or major corporate research. Kurt Ristroph is a doctoral candidate in the department of Chemical and Biological Engineering. He was awarded National Science Foundation Graduate Research Fellowship and his research focuses on polymeric nanoparticles for improved drug bioavailability, drug targeting, imaging, mucus penetration, and antimicrobial peptide delivery. Natalie Pinkerton and Hoang “Jack” Lu were doctoral students in Prof. Prud’homme’s lab. ContactsLinda JanPrinceton University Office of Technology Licensing • (609) 258-3653 • ljan@princeton.edu Laurie Tzodikov Princeton University Office of Technology Licensing • (609) 258-7256 • tzodikov@princeton.edu
*Abstract
None
*Principal Investigation

Name: Robert Prud'homme, Professor

Department: Chemical and Biological Engineering


Name: Kurt Ristroph

Department: CBE


Name: Nathalie Pinkerton, Ph.D. '14

Department: Chemical Engineering


Name: Hoang (Jack) Lu, PhD Chemical Engineering

Department: CBE

国家/地区
美国

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