New thermogelling copolymers composed of heptakis(2,6-di-O-methyl)-β-cyclodextrin, poly(propylene glycol), and poly(ethylene glycol)

Abstract

A series of new thermosensitive polyurethane copolymers composed of heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), poly(propylene glycol) (PPG), and poly(ethylene glycol) (PEG) blocks using 1,6-hexamethylene diisocyanate (HMDI) as a coupling agent were synthesized. Their chemical structures and molecular characteristics were studied using GPC analysis and 1H NMR and 13C NMR spectral analysis. We found that the copolymers had high molecular weight and the DM-β-CD, PPG, and PEG blocks were bonded by a hexamethylene dicarbamyl (HMDC) junction. DSC analysis showed that the molar motion of the PPG and PEG segments was restricted in the copolymers. Moreover, the copolymers are amphiphilic and they have very low critical micelle concentration (CMC) values ranging from 2.63–8.51 g L−1. Upon increasing temperature, the aqueous solutions of the copolymers were found to undergo a reversible clear sol–gel–turbid sol transition. The results from phase diagrams showed that the copolymers had very low critical gelation concentration (CGC) values ranging within 3–6 wt%. The copolymers synthesized in the study are easily soluble in water at room temperature, thus hydrophobic pharmaceutical agents could be entrapped into the hydrophobic cavity of CDs or loaded in the core of micelles. Then, these pharmaceutical agents are encapsulated into the gel when the copolymer forms a gel depot at around body temperature. Hence, these copolymers have potential to be used as injectable drug delivery systems.