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Updated: Dec 24, 2025
Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Biodegradable glycopolymer-b-poly(ε-caprolactone) block copolymer micelles: versatile construction, tailored lactose
Wei Chen1, Fenghua Meng, Ru Cheng
1Biomedical Polymers Laboratory, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Department of Polymer Science and Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China. j.feijen@utwente.nl zyzhong@suda.edu.cn.
Abstract:
Glycopolymer-b-poly(ε-caprolactone) (GP-PCL) block copolymer micelles ('glycomicelles') with tailored lactose functionalities were developed and investigated for hepatoma-targeted doxorubicin (DOX) delivery. Amphiphilic GP-PCL copolymers were readily prepared with controlled lactobionic acid (LBA) functionalities of 20%, 40%, 80%, and 100% (denoted as GP20-PCL, GP40-PCL, GP80-PCL, and GP100-PCL, respectively) through post-polymerization modification of the poly(acryloyl cyclic carbonate)-b-poly(ε-caprolactone) (PAC-b-PCL, 11.6-6.4 kg mol-1) block copolymer with thiolated LBA (LBA-SH) and 2-(2-methoxyethoxy)ethanethiol ((EO)2-SH) via the Michael-type addition reaction. These self-assembled glycomicelles had mean hydrodynamic diameters ranging from 31.9 to 76.8 nm depending on LBA densities, and exhibited high DOX loading efficiencies of 83.0-89.2%. In vitro release studies showed that the DOX release rate depended on the pH and LBA content. Flow cytometric analyses revealed that asialoglycoprotein receptor (ASGP-R) over-expressed HepG2 liver cancer cells following 4 h treatment with DOX-loaded glycomicelles had a 6.6-17.1-fold higher DOX level, depending on LBA densities, as compared to those treated with the corresponding DOX-loaded non-glycomicelles (100% substitution with (EO)2-SH) under otherwise the same conditions. MTT assays demonstrated that DOX-loaded GP20-PCL, GP40-PCL, GP80-PCL and GP100-PCL micelles had much lower half maximal inhibitory concentration (IC50) values of 2.05, 0.75, 0.45 and 0.43 μg DOX equiv. mL-1, respectively, in HepG2 cells than DOX-loaded non-glycomicelles (IC50: 6.55 μg mL-1 DOX equiv. mL-1). Competitive inhibition experiments showed that after the incubation with DOX-loaded glycomicelles for 4 h, more efficient killing activity against free HepG2 cells (-LBA) was observed, as compared to that against LBA-blocked HepG2 cells (+LBA) after a subsequent 72 h incubation. Glycomicelles with tailored LBA functionalities, high drug loading capacity, and high uptake by ASGP-R positive cells are promising candidates for liver cancer chemotherapy.
