Reversible cross-linked polymeric nanoplatform in drug delivery

In the past decade, polymeric micelles self-assembled from amphiphilic block copolymers have emerged as a major class of nanocarriers for drug delivery. There has been an increasing interest in using the cross-linking approach to improve the stability of conventional thermodynamic polymeric micelles. Recently, much effort has been directed to the development of reversibly cross-linked micelles that respond to endogenous and/or exogenous stimuli, in particular, pH, temperature or redox potential. Reversibly cross-linked micelles represent an ideal nanocarrier system for targeted drug delivery. These micelles exhibit superior structural stability compared to non-cross-linked counterparts. Therefore, these nanocarriers are able to minimize the premature drug release during blood circulation. The introduction of environmentally sensitive pendants to the block copolymers or the utilization of environmentally sensitive crosslinkers makes these micelles responsive to the endogenous or exogenous stimuli. The release of encapsulated drugs can be readily modulated by these stimuli. The stimuli-responsive release may result in signifi cantly enhanced therapeutic effi cacy and minimized possible side effects. This chapter focuses on the various strategies used for the design, preparation, stimuli-responsiveness and potential medical applications of reversibly cross-linked micelles for drug delivery. In vivo evidence demonstrating the effectiveness of reversibly cross-linked micelles will be presented. Lastly, future perspectives for the development of reversibly cross-linked micelle systems for drug delivery will also be explored.