Tailoring co-assembly loading of doxorubicin in solvent-triggering gel

Abstract

Noncovalent interactions are ubiquitous, endowing high feasibility on assembly and disassembly of gel network structure. Loading anticancer drugs in low molecular weight gelator (LMWG)-based gel through a noncovalently co-assembly process shows advantages of high efficacy, thixotropy, and controllable release. Drug-loaded fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F)/DMSO/H₂O-doxorubicin (DOX) gels were fabricated by an effective solvent-triggering method dominated by solvated Fmoc-F with DMSO. Density Functional Theory (DFT) calculation results show that the noncovalent interactions between Fmoc-F and DOX drive the co-assembly of the gel. DOX can assemble with Fmoc-F and realize its co-assembly loading through the H-bonding and π-π stacking, similar to the way that gel networks form. Depending on a network dis-assembly process, sustained release of DOX was achieved along with carrier decomposition through a repetitive diffusion-surface erosion process. DOX loading and release prove the non-covalent interactions and the mechanism for controlling the assembly process. By such tailoring co-assembled loading, the administration of DOX is hoped to be optimized to improve the clinical application.

Keywords: Co-assembly drug loading; Density functional theory (DFT); Disassembly release; Low molecular weight gelator (LMWG); Solvent-triggering gelation.