Regulation of drug release performance using mixed doxorubicin-doxorubicin dimer nanoparticles as a pH-triggered drug self-delivery system

• Published in: Journal of pharmaceutical analysis Vol. 12; no. 1; pp. 122 - 128
• Main Authors: Li, Jiagen, Li, Xinming, Xie, Pengwei, Liu, Peng
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.02.2022; State Key Laboratory of Applied Organic Chemistry,College of Chemistry and Chemical Engineering,Lanzhou University,Lanzhou,730000,China; Xi'an Jiaotong University; Elsevier
• Subjects: Acid-triggered release; Doxorubicin-doxorubicin dimer; Drug self-delivery system; Mixed nanoparticles; Original; Regulated drug release; Doxorubicin-doxorubicin dimer; Drug self-delivery system; Regulated drug release; Acid-triggered release; Mixed nanoparticles
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2021.03.001

A mixed drug self-delivery system (DSDS) with high drug content (>50%) was developed to regulate pH-triggered drug release, based on two doxorubicin (DOX)-DOX dimmers: D-DOXADH and D-DOXcar conjugated with acid-labile dynamic covalent bonds (hydrazone and carbamate, respectively) and stabilized with PEGylated D-DOXADH (D-DOXADH-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS. Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios. The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates. The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles. [Display omitted] •Mixed DSDS with high drug content was designed using two D-DOX dimers.•pH-Triggered release could be easily regulated by adjusting dimer feeding ratios.•Slow-release mixed DSDS nanoparticles showed high anti-tumor efficacy.