A Facile Strategy for In Situ Controlled Delivery of Doxorubicin with a pH-Sensitive Injectable Hydrogel

In light of the challenges along with the traditional intravenous administration of chemotherapeutics, injectable hydrogel-drug system emerges as a powerful tool for noninvasive and in situ controlled-release of drugs. Herein, we report a novel strategy of drug delivery system with pH responsive injectable hydrogels by taking advantages of two biomaterials. The first one is a pH sensitive polymer-drug (prodrug) conjugate, poly (ethylene glycol)–doxorubicin (MPEG–DOX) with hydrazone linkage. This prodrug interacted with a second biomaterial, α-cyclodextrin (α-CD) under mild conditions and subsequently formed the hydrogels in minutes with tunable stiffness. The gels showed a sustained release behavior dependent on the surrounding pH and released drugs effectively killed tumor cells (MCF-7). The quick cell uptake and efficient intracellular delivery of DOX were observed under a confocal microscope. This study thus provides a novel and simple drug encapsulation strategy to deliver poorly soluble drugs in situ for a potential targeted chemotherapy.