Telodendrimers for Physical Encapsulation and Covalent Linking of Individual or Combined Therapeutics

Molecular Pharmaceutics
Jason ChoiAshok Kakkar

Abstract

New therapeutics for glioblastoma multiforme and our ability to deliver them using efficient nanocarriers constitute topical areas of research. We report a comparative study of temozolomide and quercetin in the treatment of glioblastoma (GBM) in three-dimensions, and their incorporation into micelles obtained from synthetically articulated architectural copolymers, and a commercially available linear polymer poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA). A versatile synthetic methodology to telodendrimers, which can be easily adapted to the needs of other therapeutic interventions, is presented. These dendritic block copolymers self-assemble into micelles and offer a platform for single or combination drug therapy. Telodendrimer micelles loaded with quercetin did not exhibit superior cell killing effect over the free drug, but acetazolamide, an inhibitor carbonic anhydrase IX, significantly reduced GBM cell viability in 3D spheroids. Results from these studies show that high loading of drugs into telodendrimer micelles requires a physical fit between the biologically active agent and telodendrimer nanocarrier, and points toward new possibilities for incorporation of chemotherapeutic and other agents to enhance ...Continue Reading

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Citations

Oct 30, 2018·Nano Research·Yang LuZhiqiang Cao
Mar 22, 2019·Pharmaceutics·Bahman HomayunHyo-Jick Choi
Sep 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Søren Mejlsøe, Ashok Kakkar
Sep 13, 2019·Current Pharmaceutical Design·Dusica Maysinger, Jeff Ji
Feb 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hossein YazdaniAshok Kakkar
Oct 4, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dusica MaysingerAshok Kakkar
Apr 23, 2021·Pharmaceutical Development and Technology·Marija GvoicKarmen Stankov

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