Thermogel formulation for combination drug delivery
Patent Number: US20150025106
Executive Summary:
General Description:
As cancer research progresses, it is increasingly evident that single drug formulations provide only limited treatment success. Development of various and tunable combination therapies is, therefore, in high demand. One of the most important requirements of combination therapy is a simple and efficacious drug delivery system, particularly for the poorly water-soluble drugs. Many currently used chemotherapeutics are poorly water soluble, which significantly complicates the process of partnering the chemotherapeutic with a suitable delivery system. Combining two or three drugs in a formulation presents additional challenges in clinical practice because of compatibility and stability issues.
This invention provides stable solutions and thermosensitive hydrogels (thermogels) containing certain drug combinations. The system includes a water soluble biodegradable ABA-type triblock copolymer that possesses thermosensitive gelation properties. The system can form a stable thermogel that includes a combination of therapeutic agents including, for example, rapamycin, paclitaxel, and 17-AAG. After administration to a subject, the drugs are released at a controlled rate from the thermogel, which biodegrades into non-toxic components. The polymer system can also function to increase the solubility and stability of drugs in the composition. The technology has been tested in mouse model of human ovarian cancer and is ready for clinical trials.
Scientific Progress:
Soluble micelles formed from the similar compounds as are used for thermogels were shown to reduce toxicity of anti-cancer drug paxitacel (ref. 3 and 4).
Future Directions:
Strengths:
Patent Status:
Publications:
1: Cho H, Lai TC, Tomoda K, Kwon GS. Polymeric micelles for multi-drug delivery in cancer. AAPS PharmSciTech. 2015 Feb;16(1):10-20. doi: 10.1208/s12249-014-0251-3. Epub 2014 Dec 11. Review. PubMed PMID: 25501872; PubMed Central PMCID: PMC4309804.
2: McKenzie M, Betts D, Suh A, Bui K, Tang R, Liang K, Achilefu S, Kwon GS, Cho H. Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer. Pharm Res. 2016 Sep;33(9):2298-306. doi: 10.1007/s11095-016-1968-3. Epub 2016 Jun 9. PubMed PMID: 27283829.
3: Tomoda K, Tam YT, Cho H, Buehler D, Kozak KR, Kwon GS. Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer. Macromol Biosci. 2017 Jan;17(1). doi: 10.1002/mabi.201600194. Epub 2016 Jul 1. PubMed PMID: 27365266; PubMed Central PMCID: PMC5320892.
4: Tam YT, Gao J, Kwon GS. Oligo(lactic acid)n-Paclitaxel Prodrugs for Poly(ethylene glycol)-block-poly(lactic acid) Micelles: Loading, Release, and Backbiting Conversion for Anticancer Activity. J Am Chem Soc. 2016 Jul 20;138(28):8674-7. doi: 10.1021/jacs.6b03995. Epub 2016 Jul 11. PubMed PMID:
27374999.
Inventor Bio: Glen S. Kwon
https://apps.pharmacy.wisc.edu/sopdir/glen_kwon/index.php
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: https://patents.google.com/patent/US20150025106/
- Research Institute: University of Wisconsin
- Disease Focus: Cancer
- Basis of Invention: Thermosensitive hydrogels (thermogels) can be formed from water soluble, low molecular weight, biodegradable copolymers of poly(lactide-co-glycolide) and polyethylene glycol. They exist as water-based solutions at room temperature (25° C) and below. However, when the solution is heated up to the temperature of human body (37° C), the copolymers form soft solid gels
- How it works: An otherwise water-insoluble anti-cancer drug or a drug cocktail is mixed with the cold hydrogel precursor solution and injected to the tumor site. Hydrophobic hydrogel building blocks improve the solubility of therapeutic molecules. A solid hydrogel mass forms at the injection site because the injected material heats up. The therapeutic is slowly released from the gel over an extended time
- Lead Challenge Inventor: Glen S. Kwon
- Inventors: Glen S. Kwon, Hyunah Cho
- Development Stage: In vivo data in human ovarian cancer-bearing nude mice
- Novelty:
- Gel formation from the water-soluble copolymer blocks is triggered by heating the solution of copolymers to body temperature
- Solubility of hydrophobic drugs is increased by the hydrophobic copolymers
- Clinical Applications:
- Targeted delivery of therapeutics to the tumor site
- Creating various new combinations of hydrophobic, poorly soluble anti-cancer drugs
General Description:
As cancer research progresses, it is increasingly evident that single drug formulations provide only limited treatment success. Development of various and tunable combination therapies is, therefore, in high demand. One of the most important requirements of combination therapy is a simple and efficacious drug delivery system, particularly for the poorly water-soluble drugs. Many currently used chemotherapeutics are poorly water soluble, which significantly complicates the process of partnering the chemotherapeutic with a suitable delivery system. Combining two or three drugs in a formulation presents additional challenges in clinical practice because of compatibility and stability issues.
This invention provides stable solutions and thermosensitive hydrogels (thermogels) containing certain drug combinations. The system includes a water soluble biodegradable ABA-type triblock copolymer that possesses thermosensitive gelation properties. The system can form a stable thermogel that includes a combination of therapeutic agents including, for example, rapamycin, paclitaxel, and 17-AAG. After administration to a subject, the drugs are released at a controlled rate from the thermogel, which biodegrades into non-toxic components. The polymer system can also function to increase the solubility and stability of drugs in the composition. The technology has been tested in mouse model of human ovarian cancer and is ready for clinical trials.
Scientific Progress:
Soluble micelles formed from the similar compounds as are used for thermogels were shown to reduce toxicity of anti-cancer drug paxitacel (ref. 3 and 4).
Future Directions:
- Examination of more drug combinations
- Clinical trials
Strengths:
- Non-toxic, biodegradable drug delivery agent
- Solid pre-clinical validation
Patent Status:
- Filing date: 2014-07-22
- Publication date: 2015-01-22
Publications:
1: Cho H, Lai TC, Tomoda K, Kwon GS. Polymeric micelles for multi-drug delivery in cancer. AAPS PharmSciTech. 2015 Feb;16(1):10-20. doi: 10.1208/s12249-014-0251-3. Epub 2014 Dec 11. Review. PubMed PMID: 25501872; PubMed Central PMCID: PMC4309804.
2: McKenzie M, Betts D, Suh A, Bui K, Tang R, Liang K, Achilefu S, Kwon GS, Cho H. Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer. Pharm Res. 2016 Sep;33(9):2298-306. doi: 10.1007/s11095-016-1968-3. Epub 2016 Jun 9. PubMed PMID: 27283829.
3: Tomoda K, Tam YT, Cho H, Buehler D, Kozak KR, Kwon GS. Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer. Macromol Biosci. 2017 Jan;17(1). doi: 10.1002/mabi.201600194. Epub 2016 Jul 1. PubMed PMID: 27365266; PubMed Central PMCID: PMC5320892.
4: Tam YT, Gao J, Kwon GS. Oligo(lactic acid)n-Paclitaxel Prodrugs for Poly(ethylene glycol)-block-poly(lactic acid) Micelles: Loading, Release, and Backbiting Conversion for Anticancer Activity. J Am Chem Soc. 2016 Jul 20;138(28):8674-7. doi: 10.1021/jacs.6b03995. Epub 2016 Jul 11. PubMed PMID:
27374999.
Inventor Bio: Glen S. Kwon
https://apps.pharmacy.wisc.edu/sopdir/glen_kwon/index.php
