Doxorubicin Loading Capacity of Shell Cross-Linked Micelles with pH-Responsive Core as Anticancer Drug Delivery Nanocarriers

Abstract:

Detailed studies were performed to probe the effects of the cross-linking layer microstructure of pH-responsive shell cross-linked (SCL) micelles on the loading capacity of doxorubicin (DOX). Well-defined poly [(ethylene glycol)-block-2-(dimethylamino) ethyl methacrylate-block-2-(diethylamino) methacrylate] (PEG-b-P(DMA- co-QDMA)-b-PDEA) copolymer with “clickable” moieties in the middle block by the quaternization with propargyl bromide dissolved molecularly in acidic solution; micellization occurred at alkaline solution to form three-layer “onionlike” micelles constituting PDEA cores, P(DMA-co-QDMA) inner shells, and PEG coronas. Two types of cross-linker bearing azide group: 1,6-bisazidehexane and bis-(azidoethyl) disulfide were utilized to prepare the SCL micelles with different cross-linking layer microstructure via click chemistry at basic aqueous media. The results showed that two types of SCL micelles possessed excellent stability. In neutral solution, these SCL micelles still maintained structural integrity, and the average hydrodynamic diameter of SCL micelles 1 and SCL micelles 2 increased to 80 nm and 90 nm, respectively. In the acidic solution, due to the complete protonated of the PDEA core, the sizes of the two types of SCL micelles increased to 95 nm and 110 nm, respectively, which were favorable for the diffusion of the encapsulated drug in the core. Moreover, the cross-linking degree had no effect on the size of SCL micelles. The loading efficiency and loading content of the SCL micelles were significantly better than those of the uncross-linked micelles, and loading capacity did not vary with degree of cross-linking. However, the SCL micelles 1 demonstrated better loading capacity. This study could be a guidance for the future research on the effects of the cross-linking layer microstructure on controlled doxorubicin release.

• Periodical: Materials Science Forum (Volume 898)
• Pages: 2366-2372
• DOI: https://doi.org/10.4028/www.scientific.net/MSF.898.2366
• Online since: June 2017
• Authors: Shu Yu Zhu, Zhong Li Niu, Xiao Ting Zhang, Dan Yue Wang, Jia Ming Xu, Bin Sun, Mei Fang Zhu, Xiao Ze Jiang*
• Keywords: Doxorubicin, Layer Microstructure, Loading Capacity, pH-Responsive Triblock Copolymer, Shell Cross-Linked Micelles

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