IJMS, Vol. 26, Pages 5866: Self-Assembling Amphiphilic ABA Triblock Copolymers of Hyperbranched Polyglycerol with Poly(tetrahydrofuran) and Their Nanomicelles as Highly Efficient Solubilization and Delivery Systems of Curcumin

International Journal of Molecular Sciences doi: 10.3390/ijms26125866

Authors:
Dóra Fecske
György Kasza
Gergő Gyulai
Kata Horváti
Márk Szabó
András Wacha
Zoltán Varga
Györgyi Szarka
Yi Thomann
Ralf Thomann
Rolf Mülhaupt
Éva Kiss
Attila Domján
Szilvia Bősze
Laura Bereczki
Béla Iván

Delivering of hydrophobic drugs by polymeric nanoparticles is an intensively investigated research and development field worldwide due to the insufficient solubility of many existing and potential new drugs in aqueous media. Among polymeric nanoparticles, micelles of biocompatible amphiphilic block copolymers are among the most promising candidates for solubilization, encapsulation, and delivery of hydrophobic drugs to improve the water solubility and thus the bioavailability of such drugs. In this study, amphiphilic ABA triblock copolymers containing biocompatible hydrophilic hyperbranched (dendritic) polyglycerol (HbPG) outer and hydrophobic poly(tetrahydrofuran) (PTHF) inner segments were synthesized using amine-telechelic PTHF as a macroinitiator for glycidol polymerization. These hyperbranched–linear–hyperbranched block copolymers form nanosized micelles with 15–20 nm diameter above the critical micelle concentration. Coagulation experiments proved high colloidal stability of the aqueous micellar solutions of these block copolymers against temperature changes. The applicability of block copolymers as drug delivery systems was investigated using curcumin, a highly hydrophobic, water-insoluble, natural anti-cancer agent. High and efficient drug solubilization up to more than 3 orders of magnitude to that of the water solubility of curcumin (>1500-fold) is achieved with the HbPG-PTHF-HbPG block copolymer nanomicelles, locating the drug in amorphous form in the inner PTHF core. Outstanding stability of and sustained curcumin release from the drug-loaded block copolymer micelles were observed. The in vitro bioactivity of the curcumin-loaded nanomicelles was investigated on U-87 glioblastoma cell line, and an optimal triblock copolymer composition was found, which showed highly effective cellular uptake and no toxicity. These findings indicate that the HbPG-PTHF-HbPG triblock copolymers are promising candidates for advanced drug solubilization and delivery systems.

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