title: The challenges facing block copolymer micelles for cancer therapy: In vivo barriers and clinical translation.
abstract: 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.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada. Electronic address: sina.eetezadi@mail.utoronto.ca.
authors.forename: Sina
authors.initials: S
authors.lastname: Eetezadi
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada. Electronic address: sandra.ekdawi@mail.utoronto.ca.
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Ekdawi
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada; Techna Institute, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 124-100 College Street, Toronto, Ontario M5G 1P5, Canada. Electronic address: cj.allen@utoronto.ca.
authors.forename: Christine
authors.initials: C
authors.lastname: Allen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D008823:Micelles; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers
keywords: Cancer heterogeneity; EPR; Experimental models; Nano drug delivery systems; Nanoformulation; Nanomedicines; Tumor drug bioavailability; Tumor penetration