pH-Sensitive Nanoparticles for Drug Delivery
Patent Number: US9687563
Executive Summary:
General Description:
Many agents used for oncology are either vulnerable to enzymatic attack or are poorly water-soluble, making them difficult to deliver to a tumor site. This invention describes a novel pH-sensitive peptide-based nanoparticle which can provide a precisely targeted method for drug delivery. Rather than relying on uptake of the nanoparticle into the tumor, this invention exploits the weakly acidic (pH ~ 7) microenvironment near a tumor to dissolve a pH-sensitive peptide and release the agent directly at the tumor site. Materials prone to enzymatic attack and poorly water soluble agents can be protected until they reach the target location. The peptide then releases the agent at the tumor location where the pH is ≤ 7. This formulation provides much greater pH sensitivity than other currently available drug-delivery nanoparticles, which all require a much more acidic transition pH (4-5). In-vivo tests on mice have demonstrated non-toxicity and effectiveness at slowing tumor growth. Animal subjects treated with the pH-sensitive nanoparticles showed slower tumor growth when compared to control treatment methods, even at 1/10th the control dosage. The particle formulation is highly adaptable, can carry a variety of drugs as well as RNA/DNA, and can be “tuned” to dissolve at a specific pH.
Scientific Progress:
Future Directions:
Strengths:
Weaknesses:
Publications:
Choi, H., Liu, T., Nath, K., Zhou, R., & Chen, I. W. (2017). Peptide nanoparticle with pH-sensing cargo solubility enhances cancer drug efficiency. Nano Today, 13, 15-22. http://www.sciencedirect.com/science/article/pii/S1748013216303498
Patent Status:
Legal status – Issued US Patent (9,687,563), 1 pending continuation (15/595,135)
Inventor Bio: I-Wei Chen, Rong Zhou
http://www.seas.upenn.edu/~iweichen/
http://www.med.upenn.edu/apps/faculty/index.php/g334/p4498
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: 1 issued US patent, 1 pending US continuation application
- Patent Link: https://www.google.com/patents/US9687563/
- Research Institute: University of Pennsylvania
- Disease Focus: Cancer
- Basis of Invention: engineered nanoparticle drug delivery
- How it works: pH sensitive peptides dissolve at the tumor site and release a drug
- Lead Challenge Inventor: I-Wei Chen
- Inventors: I-Wei Chen, Rong Zhou
- Development Stage: Pre-clinical (mouse model)
- Novelty: Targeted delivery to tumor sites for drug release
- Clinical Applications: Cancer
General Description:
Many agents used for oncology are either vulnerable to enzymatic attack or are poorly water-soluble, making them difficult to deliver to a tumor site. This invention describes a novel pH-sensitive peptide-based nanoparticle which can provide a precisely targeted method for drug delivery. Rather than relying on uptake of the nanoparticle into the tumor, this invention exploits the weakly acidic (pH ~ 7) microenvironment near a tumor to dissolve a pH-sensitive peptide and release the agent directly at the tumor site. Materials prone to enzymatic attack and poorly water soluble agents can be protected until they reach the target location. The peptide then releases the agent at the tumor location where the pH is ≤ 7. This formulation provides much greater pH sensitivity than other currently available drug-delivery nanoparticles, which all require a much more acidic transition pH (4-5). In-vivo tests on mice have demonstrated non-toxicity and effectiveness at slowing tumor growth. Animal subjects treated with the pH-sensitive nanoparticles showed slower tumor growth when compared to control treatment methods, even at 1/10th the control dosage. The particle formulation is highly adaptable, can carry a variety of drugs as well as RNA/DNA, and can be “tuned” to dissolve at a specific pH.
Scientific Progress:
- Shown in-vivo to be more effective than control treatments, even at 1/10th the dosage
Future Directions:
- Test with additional drugs and indications
Strengths:
- High sensitivity to incremental pH-changes allows more precise targeting of tumors
- Hydrophobic barriers protect agents until they are delivered to the target site
- Wide adaptability of method means that a variety of agents can be carried and protected, including RNA/DNA and poorly water-soluble drugs
Weaknesses:
- Further in-vivo study needed
Publications:
Choi, H., Liu, T., Nath, K., Zhou, R., & Chen, I. W. (2017). Peptide nanoparticle with pH-sensing cargo solubility enhances cancer drug efficiency. Nano Today, 13, 15-22. http://www.sciencedirect.com/science/article/pii/S1748013216303498
Patent Status:
Legal status – Issued US Patent (9,687,563), 1 pending continuation (15/595,135)
- Priority date – 8/26/2013
- Filing date – 8/26/2013
- Publication date – 7/28/2016
- Grant date – 6/27/2017
Inventor Bio: I-Wei Chen, Rong Zhou
http://www.seas.upenn.edu/~iweichen/
http://www.med.upenn.edu/apps/faculty/index.php/g334/p4498
