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Updated: Jul 12, 2026

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
Programmed drug delivery system based on optimized "size decrease and hydrophilicity/hydrophobicity transformation"
Yuanyuan Liu1, Lian Li1, Lijia Li1
1Key Laboratory of Drug Targeting and Drug Delivery System (Ministry of Education), West China School of Pharmacy, Sichuan University, No. 17, Block 3, South Renmin Road, Chengdu 610041, P.R. China.
Abstract:
Requirements on drug delivery systems to surmount a complex series of pathophysiological barriers bear "cascading contradictions", especially size and hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery system (GNPs-Dox-Lac) based on optimized "size decrease and hydrophilicity/hydrophobicity transformation" was developed by combination the gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood circulation and inclined to accumulate at the tumor site. Then the degradation of the GNPs triggered by tumor extracellular matrix metalloproteinase-2 (MMP2) led to the release of prodrug Dox-Lac (Mw 898 Da) to facilitate the tumor tissue penetration and cellular uptake. Last, pH-responsive disassociation of Dox-Lac in tumor cells resulted in the free Dox (Mw 543 Da) release to induce toxicity. As expected, GNPs-Dox-Lac achieved superior tumor inhibition rate of 90.8% with low toxicity in vivo, suggesting its potential for enhanced hepatocellular carcinoma (HCC) therapy of doxorubicin in future.
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