Enhanced DOX loading in star‐like benzyl functionalized polycaprolactone micelles

Abstract

AbstractThe self‐assembly of functionalized polycaprolactone amphiphilic diblock copolymers is explored for carrier‐mediated doxorubicin delivery for cancer treatment. In this report, functionalized polycaprolactone‐based amphiphilic block copolymers with controlled branching architecture are investigated. Star‐like copolymers, namely 4‐arm and 6‐arm poly(γ‐benzyloxy‐ε‐caprolactone)‐b‐poly{γ‐2‐[2‐(2‐methoxyethoxy)ethoxy]ethoxy‐ε‐caprolactone} (PBCL‐b‐PMEEECL) were synthesized by living ring‐opening block copolymerization (ROP) of γ‐(2‐benzyloxy)‐ε‐caprolactone and γ‐2‐[2‐(2‐methoxyethoxy)ethoxy]ethoxy‐ε‐caprolactone using multifunctional initiators. A systematic investigation of the effect of branching points on polymer properties and micellar carrier properties was carried out. The star‐like PBCL‐b‐PMEEECL micelles displayed better thermodynamic stability, size reduction, and enhanced doxorubicin encapsulation than the linear PBCL‐b‐PMEEECL. Furthermore, the π–π stacking between the benzyl group of the hydrophobic PBCL core and the doxorubicin, the anti‐cancer drug, also increases the stability and loading capacity of the micelles. The star‐polymers display tunable thermoresponsivity in the range of 40–42°C. When the DOX‐loaded micelles are accumulated in the tumor, the shell of the polymeric micelles dehydrates upon heating (at a temperature above its LCST), causing disassembling of the micelles and releasing of DOX. Compared with DOX‐loaded linear and 4‐arm micelles, DOX‐loaded 6‐arm micelles exhibited higher in vitro anti‐tumor activity. Thus, the 6‐arm benzyl substituted polycaprolactone‐based micellar systems are promising candidates for drug delivery applications.