A suite of nanocarrier technologies that provide targeted drug delivery of hydrophobic and hydrophilic drugs to specific disease sites.
Background: Delivery of therapeutic and diagnostic compounds is limited by the lack of efficient carriers to improve in vivo stability, selectivity as well as to reduce immunogenicity. Conventional nanocarrier design generally follows a “trial and error” approach using a limited number nanoparticle types to fit a variety of drug molecules that exhibit substantial chemical variation. This approach results in suboptimal nano-formulations with compromised efficiency for in vivo drug delivery and decreased probability of successful clinical translation. In contrast, the suite of innovations described herein offer a customized nanocarrier platform with the capability of structure-based design and systematic optimization to bridge the gap for nanomedicine in clinical translation.
Technology Overview: This innovative technology portfolio from Upstate Medical University provides multiple chemical formulations of telodendrimer nanoparticles made from biocompatible polyethylene glycol, amino acids, and natural compounds. The resulting nanoparticles results in the biocompatible and effective delivery of various therapeutic drugs for targeted disease treatments. Telodendrimer refers to a linear-dendritic copolymer, containing a hydrophilic segment (i.e., PEG or poly/oligo zwitterionic moieties) and one or more dendritic domain with the peripheries covalently conjugated with well-defined chemical moieties selected based on the affinities specifically to the drug molecule to be delivered. Such end groups are selected based on the chemical structure of the chosen therapeutic drug and can be optimized via a systematic combinatorial approach. Drugs that can be sequestered in the customized nanocarriers or linked to the conjugates include, but are not limited to, anticancer drugs: taxanes, Doxorubicin, Platinum drugs, topoisomerase II inhibitors, topoisomerase I inhibitors, tubulin interacting agents, hormonal agents, thymidylate synthase inhibitors, anti-metabolites, alkylating agents, aromatase inhibitors, and antibiotics: e.g. polymyxin, gentamycin, tetracycline drugs, amphotericin, and immune-modulating drugs: methotrexate, dexamethasone, curcumin, tetracycline and derivatives, etc. http://suny.technologypublisher.com/files/sites/110-2024.jpg Advantages: • Stable drug formulations with small nanoparticle sizes (20-30 nm); • In vitro and in vivo extended half-life stability; • Efficient disease targeting drug delivery; • Capability for intracellular delivery; • Capability for encapsulating high amounts of drug molecules (10%-100% of drug/nanoparticles by weight); • The ability to protect bioactivity with reduced toxicity of current cancer treatments; • Well-defined structure for reproducibility; and • Provides a systematic approach for nanocarrier optimization based on drug structure to meet FDA regulations and thereby improve potential for clinical translation.
Applications: • Drug Delivery for hyperproliferative disorders including cancer • Delivery of antibiotics for infectious disease • Drug delivery for other disorders including inflammatory or allergic diseases, autoimmune diseases, graft rejection and other diseases where undesired inflammatory responses need to be inhibited Intellectual Property Summary: • Functional Segregated Telodendrimers and Nanocarriers and Methods of Making and Using the Same - US 2017/0252456 A1 • Telodendrimers with Riboflavin Moieties and Nanocarriers and Methods of Making and Using the Same - WO2018136778A1 and US20190328742A1 • Zwitterionic Dendritic Amphiphiles, Zwitterionic Dendrimers, Zwitterionic Telodendrimers, Nanocarriers Comprising the Same, and Methods of Making and Using the Same - WO2018160759A1 and US20200009069A1 • Telodendrimers and Nanocarriers and Methods of Using the Same: EP3035968B1 and U.S.20150056139A1 Stage of Development: In vivo and ex vivo studies in cancer and inflammation mouse models have been completed. Licensing Status: Seeking an industry partner to license the technology or partner to further technical development. Additional Information: • Guo, D., Shi, C., Wang, L., Ji, X., Zhang, S. & Luo, J.* Rationally Designed Micellar Nanocarriers for the Delivery of Hydrophilic Methotrexate in Psoriasis Treatment. ACS Applied Bio Materials (2020), 3, 8, 4832–4846. https://pubs.acs.org/doi/10.1021/acsabm.0c00342 • Guo D, Shi C, Wang X, Wang L, Zhang S, Luo J.* Riboflavin- containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy. Biomaterials. 2017 Oct;141:161-175. https://www.sciencedirect.com/science/article/pii/S0142961217304489?via%3Dihub • Wang L, Shi C, Wright FA, Guo D, Wang X, Wang D, Wojcikiewicz RJH, Luo J.* Multifunctional Telodendrimer Nanocarriers Restore Synergy of Bortezomib and Doxorubicin in Ovarian Cancer Treatment. Cancer Res. 2017 Jun 15;77(12):3293-3305. https://cancerres.aacrjournals.org/content/77/12/3293.lon • Shi C, Guo D, Xiao K, Wang X, Wang L, Luo J.* A drug-specific nanocarrier design for efficient anticancer therapy. Nat Commun. 2015 Jul 9;6:7449. doi: 10.1038/ncomms8449. https://www.nature.com/articles/ncomms8449 • Xu G, Shi C, Guo D, Wang L, Ling Y, Han X, Luo J.* Functional- segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment. Acta Biomater. 2015 Jul;21:85-98. doi: 10.1016/j.actbio.2015.04.021. https://www.sciencedirect.com/science/article/abs/pii/S1742706115001920?via%3Dihub • Huang W, Wang X, Shi C, Guo D, Xu G, Wang L, Bodman A, Luo J.* Fine-tuning vitamin E-containing telodendrimers for efficient delivery of gambogic acid in colon cancer treatment. Mol Pharm. 2015 Apr 6;12(4):1216-29. doi: 10.1021/acs.molpharmaceut.5b00051. https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5b00051 • Cai L, Xu G, Shi C, Guo D, Wang X, Luo J.* Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: A synergistic combination nanotherapy for ovarian cancer treatment. Biomaterials. 2015 Jan; 37:456-468. doi: 10.1016/j.biomaterials.2014.10.044. https://www.sciencedirect.com/science/article/pii/S0142961214010928?via%3Dihub • Shao Y, Shi C, Xu G, Guo D, Luo J.* Photo and redox dual responsive reversibly cross-linked nanocarrier for efficient tumor- targeted drug delivery. ACS Appl Mater Interfaces. 2014 Jul 9;6(13):10381-92. doi: 10.1021/am501913m. https://pubs.acs.org/doi/10.1021/am50191