Back to Search Start Over

Mesoscopic Simulations of Diselenide-Containing Crosslinked Doxorubicin-Loaded Micelles and Their Tumor Microenvironment Responsive Release Behaviors

Authors :
Wenjing Lin
Jieheng Zhang
Fusheng Zhang
Wensheng Wu
Feihua Chen
Zikang Zhang
Xiaofeng Lin
Chufen Yang
Guobin Yi
Source :
Journal of Pharmaceutical Sciences. 112:1388-1400
Publication Year :
2023
Publisher :
Elsevier BV, 2023.

Abstract

There is currently limited research on the structure-property relationship of reduction stimuli-responsive polymeric crosslinked micelles using mesoscopic simulations. Herein, dissipative particle dynamics (DPD) simulations were used to simulate the self-assembly process of the blank non-crosslinked micelle, the structure and doxorubicin (DOX) distribution of diselenide crosslinked micelle with different crosslinker contents (CCs) based on the nearest-neighbor bonding principle. The results revealed that the formation of a three-layer spherical micelle and the loaded DOX mainly distributed in the polycaprolactone (PCL) core and hydroxyethyl methacrylate (HEMA) mesosphere. The larger the dosage of DOX, the more DOX encapsulated, but the encapsulation of DOX in the hydrophobic domain would reach saturation when the dosage increased to 6.0 %. In micelles with lower CCs or crosslinking levels (CLs), DOX entered the middle layer and the inner core faster. Then, based on the nearest media-bead bond breaking principle and subsequently DPD simulation, the effects of different CCs on the micelle structure and DOX release properties were investigated. Low CC could cause fast drug release. With the increase of CCs, the micelle showed a slower DOX release trend. The multilayer crosslinked network system also affected the DOX release rate. Hence, this work can provide some mesoscale guidance for the structural design and structure-property relationship of stimuli-responsive reversible crosslinked micelles for drug delivery.

Subjects

Subjects :
Pharmaceutical Science

Details

ISSN :
00223549
Volume :
112
Database :
OpenAIRE
Journal :
Journal of Pharmaceutical Sciences
Accession number :
edsair.doi.dedup.....e1cb306c30084ae8a6b2de79326c3996
Full Text :
https://doi.org/10.1016/j.xphs.2022.12.015