Substrate delivery of embedded liposomes
Patent Number: WO2017031060
Executive Summary:
General Description:
The ability to control the location and release rate of therapeutic agents remains a central challenge for biomedical research. The drugs are released slowly and steadily, in a controlled fashion, when a therapeutic cargo is attached to a solid carrier (immobilized). While liposomes have become the most widely researched, tested, and commercialized nanocarrier system, their immobilization to a solid surface remains a challenge. The reason for the this is the dynamic nature of the lipid bilayer forming the liposome: instead of intact liposome immobilization, liposomes tend to fuse to the solid substrate.
The inventors covalently functionalized the liposomes with hyaluronic acid to promote their immobilization in intact form. These hyaluronic acid-containing liposomes form ionic interactions with a polyelectrolyte multilayer and are efficiently embedded in it. Another polyelectrolyte multilayer formed on top of the immobilized liposomes completes the liposome immobilization, supports cell adhesion, and provides control over the release of both the therapeutic encapsulated in the liposomes. The resulting substrate-mediated drug delivery system has modulated the cytotoxic effect of doxorubicin toward the patient-derived metastatic breast cancer cells. Moreover, the drug uptake was localized to the cells immobilized on the solid liposome carrier for up to 60 hours, proving that the local delivery of an active therapeutic is possible with the liposome-embedded polyelectrolyte multilayer platform.
Scientific Progress:
Liposomes coated with hyaluronic acid were used for delivery of therapeutic microRNA to metastatic breast cancer cell line (ref. 2).
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Publications:
1."Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells”, Stephen Hayward, Christina Wilson, Srivatsan Kidambi, OncoTarget, 2016
2.Targeted Delivery of MicroRNA-125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 positive Metastatic Breast Cancer”, Stephen Hayward, David Francis, Parviz Kholmatov, Srivatsan Kidambi, Journal of Biomedical Nanotechnology, 2016 doi: 10.1166/jbn.2016.2194
3.“Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery”, Stephen Hayward, David Francis, Matthew Sis, Srivatsan Kidambi, Nature Scientific Reports, 2015, doi: 10.1038/srep14683
Inventor Bio: Srivastan Kidambi
http://engineering.unl.edu/chme/srivatsan-kidambi/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Patent pending
- Patent Link: https://www.google.com/patents/WO2017031060
- Research Institute: University of Nebraska
- Disease Focus: Cancer
- Basis of Invention: Liposomes are nanoparticles that efficiently encapsulate a variety of therapeutic agents and release them inside the target cells. Localized and sustained release of many anti-cancer therapeutic agents (including liposomes) may be achieved by attaching them to a solid carrier and implanting the carrier next to the tumor site. Liposomes coated with hyaluronic acid can be immobilized to a polyelectrolyte multilayer
- How it works: Liposomes carrying anti-cancer drug doxorubicin are attached to the solid polyelectrolyte film. Another layer of the film is deposited on top of the liposomes. Cancer cells are seeded on the resulting structure and their viability is monitored. For clinical applications, the embedded liposomes can be implanted or coated onto a stent or surgical instrument. Doxorubicin may be substituted by any anti-cancer agent
- Lead Challenge Inventor: Srivastan Kidambi
- Inventors: Srivatsan Kidambi, Stephen L. Hayward
- Development Stage: In vitro data in patient-derived metastatic cancer cells
- Novelty:
- Immobilization of liposomes in solid phase
- Clinical Applications:
- Post-surgical implants in cancer and other diseases
- Stent-based gene or drug delivery
- Transcutaneous vaccine delivery
General Description:
The ability to control the location and release rate of therapeutic agents remains a central challenge for biomedical research. The drugs are released slowly and steadily, in a controlled fashion, when a therapeutic cargo is attached to a solid carrier (immobilized). While liposomes have become the most widely researched, tested, and commercialized nanocarrier system, their immobilization to a solid surface remains a challenge. The reason for the this is the dynamic nature of the lipid bilayer forming the liposome: instead of intact liposome immobilization, liposomes tend to fuse to the solid substrate.
The inventors covalently functionalized the liposomes with hyaluronic acid to promote their immobilization in intact form. These hyaluronic acid-containing liposomes form ionic interactions with a polyelectrolyte multilayer and are efficiently embedded in it. Another polyelectrolyte multilayer formed on top of the immobilized liposomes completes the liposome immobilization, supports cell adhesion, and provides control over the release of both the therapeutic encapsulated in the liposomes. The resulting substrate-mediated drug delivery system has modulated the cytotoxic effect of doxorubicin toward the patient-derived metastatic breast cancer cells. Moreover, the drug uptake was localized to the cells immobilized on the solid liposome carrier for up to 60 hours, proving that the local delivery of an active therapeutic is possible with the liposome-embedded polyelectrolyte multilayer platform.
Scientific Progress:
Liposomes coated with hyaluronic acid were used for delivery of therapeutic microRNA to metastatic breast cancer cell line (ref. 2).
Future Directions:
- Pre-clinical animal trials
Strengths:
- Versatile nanocarrier system based on commonly available reagents
Weaknesses:
- No animal data
Patent Status:
- Priority date: 2015-08-14
- Application date: 2017-02-23
Publications:
1."Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells”, Stephen Hayward, Christina Wilson, Srivatsan Kidambi, OncoTarget, 2016
2.Targeted Delivery of MicroRNA-125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 positive Metastatic Breast Cancer”, Stephen Hayward, David Francis, Parviz Kholmatov, Srivatsan Kidambi, Journal of Biomedical Nanotechnology, 2016 doi: 10.1166/jbn.2016.2194
3.“Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery”, Stephen Hayward, David Francis, Matthew Sis, Srivatsan Kidambi, Nature Scientific Reports, 2015, doi: 10.1038/srep14683
Inventor Bio: Srivastan Kidambi
http://engineering.unl.edu/chme/srivatsan-kidambi/
