Injectable hydrogels by inclusion complexation between a three-armed star copolymer (mPEG-acetal-PCL-acetal-)3 and α-cyclodextrin for pH-triggered drug delivery

We recently reported a precise modular synthesis technique and structure-property study, in which a series of acid-cleavable star-block copolymers containing poly(ethylene glycol) monomethyl ether (mPEG) and poly(epsilon-caprolactone) (PCL) blocks linked with acid-cleavable acetal groups, abbreviated as (mPEG-a-PCL-a-)(3), were prepared and characterized. In this paper, we focus on developing the acid-cleavable star-block copolymer into an injectable hydrogel that is based on inclusion complexes between (mPEG-a-PCL-a-)(3) and alpha-cyclodextrin (alpha-CD). The gelation times for the hydrogels were tested by a vial-tilting method, and the results indicated that these gels have a fast gelation process. Wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) analyses were utilized to study the formation of necklace-like crystalline inclusion complexes between PEG-containing polymers and alpha-CD. Scanning electron microscopy (SEM) observation results showed that these lyophilized hydrogels with different components mainly exhibited a porous spongelike structure. Good structure recovery properties of the supramolecular hydrogels, which were identified by rheological tests, indicate that these hydrogels have great potential application in the area of injectable hydrogels. These supramolecular hydrogels show flowable characters under a large stress, and the hydrogel systems exhibit unique structure-related reversible gel-sol transition properties at a certain stress. After removal of the high shear stress, the network structures of the sol solutions started being restored immediately. Furthermore, these hydrogels are essentially elastic in response to small stresses over a frequency range that covers everyday activities such as walking and running. Doxorubicin hydrochloride (DOX center dot HCl), as a model drug, was encapsulated into the hydrogels, and was then released from the drug-loaded hydrogels because the acetal groups possess pH-triggered fracture behavior. It is expected that this kind of injectable hydrogel has promising applications in the treatment of joint disease.