Burst Release of Lipophilic Drugs from Poly (Ethylene Oxide)- B-Polystyrene Micelles is not Caused by Micelle Disassembly

Abstract

Burst release is one of the challenges which limit clinical successes of block copolymer micelles for targeted delivery of lipophilic anticancer drugs. It’s generally assumed that burst drug release in blood circulation is mainly due to blood dilution and subsequent micelle disassembly after i.v. administration. Hence, investigating the integrity of polymeric micelles is therefore essential to understanding the mechanisms of burst release. In this study, lipophilic cargo was observed to be rapidly released from poly(ethylene oxide)-b-polystyrene (PEG-PS) micelles into PC-3 and MDA-MB-231 cancer cells before the micelles were internalized into cells. Fluorescence resonance energy tranfer (FRET) imaging and fluorescence quecnhing by iron oxide nanoparticles (IONPs) were used to assess in vitro and in vivo integrity of PEG-PS micelles. The results showed that the disassembly of PEG-PS micelles in cell culture media and fetal bovine serum was very limited over 24 h. When PEG-PS micelles were internalized into cancer cells, a majority of internalized PEG-PS micelles kept integrity. Rapid in vivo disassembly of micelles upon blood dilution was not observed and the micelles in mouse body gradually disassembled over 24 h. In summary, burst release of lipophilic drugs from PEG-PS micelles was not caused by micelle disassembly. This finding is useful for developing polymeric micelles with controlled release of lipophilic drugs.