The challenges facing block copolymer micelles for cancer therapy: In vivo barriers and clinical translation

The application of block copolymer micelles (BCMs) in oncology has benefitted from advances in polymer chemistry, drug formulation and delivery as well as in vitro and in vivo biological models. While great strides have been made in each of these individual areas, there remains some disappointment overall, citing, in particular, the absence of more BCM formulations in clinical evaluation and practice. In this review, we aim to provide an overview of the challenges presented by in vivo systems to the effective design and development of BCMs. In particular, the barriers posed by systemic administration and tumor properties are examined. The impact of critical features, such as the size, stability and functionalization of BCMs is discussed, while key pre-clinical endpoints and models are critiqued. Given clinical considerations, we present this work as a means to stimulate a renewed focus on the unique chemical versatility bestowed by BCMs and a measured grasp of representative in vitro and in vivo models. (C) 2014 Elsevier B.V. All rights reserved.