1. Tarbiat Modares University 2. Tarbiat modares university
Abstract
Introduction
A variety of nano-systems constituted by polymer–drug conjugates have been designed to overcome its shortages on water solubility, chemical instability, and poor bioavailability. however, most of them suffer from ineffective release of doxorubicin in cancer cells in vivo. this work developed a novel flexible acid-responsive micelle formulation by covalently conjugating dox on the hydrophilic terminals of pluronic f127 chains via succinic anhydride linkers.
Methods
The main materials used in this study include pluronic f127, doxorubicin, succinic anhydride and dimethyl sulfoxide. the anticancer drug doxorubicin was covalently bound to f127 through amide group susceptible to lysosomal hydrolysis. the structures of f127 polymer and f127-suc-dox conjugate were characterized using ft-ir spectrophotometer. f127-suc-dox micelles were prepared by the self-assembly using ultrasonic emulsification technology. then the particle size of f127-suc-dox micelles were determined by dynamic light scattering (dls).
Results
The ft-ir spectra of f127, f127-suc and f127-suc-dox confirmed the successful linkage of f127, succinic anhydride and doxorubicin. to reveal the ph-sensitive property of micelles caused by succinic anhydride cleavage in acidic conditions, changes in particle size of micelles from ph 7.4 to ph 5.0 were monitored. at ph 5.0, the average size of micelles increased from 30nm to 140nm during 24h.
Conclusion
A novel acid-responsive pluronic f127-suc-dox conjugate micelle was developed. doxorubicin was covalently linked to the hydrophilic segment of pluronic f127 through ph-sensitive succinic anhydride linkage as the pendants in the chain. the amphiphilic f127-suc-dox self-assembled into micelles with suitable size. particle size of micelles increased in acidic condition.
