Micelles based on methoxy poly(ethylene glycol)-cholesterol conjugate for controlled and targeted drug delivery of a poorly water soluble drug.
In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4.0 x 10(-7) M - 13 x 10(-7) M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QC-loaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Junming
J
Li
Zhiyao
Z
He
Shui
S
Yu
Shuangzhi
S
Li
Qing
Q
Ma
Yiyi
Y
Yu
Jialin
J
Zhang
Rui
R
Li
Yu
Y
Zheng
Gu
G
He
Xiangrong
X
Song
D002784:Cholesterol / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D008823:Micelles; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions; D014867:Water / Q000737:chemistry*
D003692:Delayed-Action Preparations; D008823:Micelles; D004364:Pharmaceutical Preparations; D013535:Suspensions; D014867:Water; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002784:Cholesterol