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

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 their effectiveness.

• Authors: Jason Choi, Alexandre Moquin, Enzo Bomal, Li Na, Dusica Maysinger, Ashok Kakkar
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 14 Issue 8 Pg. 2607-2615 (08 07 2017) ISSN: 1543-8392 [Electronic] United States
• PMID: 28520445 (Publication Type: Journal Article)

Chemical References

• Dendrimers
• Lactates
• Micelles
• Polyesters
• poly(lactic acid-ethylene glycol)
• polyethylene glycol-poly(lactide-co-glycolide)
• Polyethylene Glycols
• Dacarbazine
• Quercetin
• Carbonic Anhydrase IX
• Acetazolamide
• Temozolomide

Topics

• Acetazolamide (chemistry, pharmacology)
• Carbonic Anhydrase IX (antagonists & inhibitors)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dacarbazine (analogs & derivatives, chemistry, pharmacology)
• Dendrimers (chemistry)
• Drug Delivery Systems (methods)
• Glioblastoma (metabolism)
• Humans
• Lactates (chemistry)
• Micelles
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Quercetin (chemistry, pharmacology)
• Spheroids, Cellular (cytology, metabolism)
• Temozolomide