Polymeric micelles have been widely used as ideal drug-delivery vehicles with unique advantages. However, fine tuning of the degradation rates of micelles over a wide time frame remains challenging. Herein, we designed and synthesized a novel pH-responsive, hydrophobic epoxide monomer, tetrahydrofuranyl glycidyl ether (TFGE), carrying an acetal group as a cleavable linkage. The hydrolysis kinetics of TFGE was carefully evaluated with representative functional epoxide monomers, such as 1-ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether, via in situ 1H NMR spectroscopy and quantum mechanical calculations. Interestingly, the hydrolysis kinetics and the associated energy barrier were closely related not only to the cyclic/acyclic structure of the monomers but also to their hydrophobicity. Subsequently, a series of amphiphilic block copolymers (mPEG-b-PTFGE) were synthesized via anionic ring-opening polymerization and the self-Assembled polymeric micelles were evaluated with respect to critical micelle concentration, encapsulation efficiency, drug release, and cell viability. Most notably, the release kinetics of the model compound from polymeric micelles exhibited a different trend, confirming the critical role of hydrophobicity in governing the pH-responsive hydrolysis of the polymeric micelles. This study provides new insights applicable to the design of functional monomers for tailoring the release profiles of polymeric micelles for smart drug delivery. ©
Bibliographical noteFunding Information:
The authors thank Tae-young Heo in Hongik University for useful comments and measurement of DLS, and Dongseok Kim in Yonsei University for measurement of AFM. This work was supported by the National Research Foundation of Korea (NRF-2017R1A2B3012148). C.G.L. acknowledges the support from the Global Ph.D. fellowship program through the National Research Foundation of Korea (NRF) (NRF-2018H1A2A1061237).
Copyright © 2019 American Chemical Society.
All Science Journal Classification (ASJC) codes
- Organic Chemistry
- Polymers and Plastics
- Inorganic Chemistry
- Materials Chemistry