Redox-responsive self-assembly polymeric micelles based on mPEG-β-cyclodextrin and a camptothecin prodrug as drug release carriers

doi:10.5246/jcps.2021.12.081

Abstract

Abstract:

Stimuli-responsive drug delivery systems based on polymeric micelles can achieve controlled drug release to improve the therapeutic outcome and reduce unwanted systematic toxicity and side effects of the cytotoxic drug in chemotherapy but often face challenging synthesis and purification of functionalized biocompatible polymer materials and low drug loading efficiency. In the present study, we reported a novel redox-responsive self-assembly polymeric micelle system, mPEG-β-CD/Ad-SS-CPT, to achieve high loading efficiency and selective delivery of camptothecin (CPT) in a reductive environment inside cancer cells. The host-guest supramolecular micelles utilized a simple β-CD modified PEG, mPEG-β-cyclodextrin (mPEG-β-CD), as the polymeric host with the ease of synthesis and purification. The guest prodrug Ad-SS-CPT contained the disulfide bond as the redox sensitivity group. The selective cleavage of disulfide bond and subsequent drug release in a reductive environment could potentially reduce system toxicity and improve the therapeutic outcome of CPT. In vitro studies showed that the micelles exhibited excellent cytotoxicity against HeLa cells comparable to the free drug. The host-guest polymeric micelles also showed great potentials for multi-drug co-delivery. Collectively, our current findings provided a general and convenient approach to design drug delivery systems based on stimuli-responsive polymeric micelles for disease treatment.

Key words: mPEG-β-cyclodextrin, Camptothecin prodrug, Self-assembled micelles, Redox-responsive, Supramolecular

Supporting:

Yiben Lu, Miao Zhang, Yongjun Zheng, Xinyu Hou, Muye He, Kaiyan Lou, Feng Gao. Redox-responsive self-assembly polymeric micelles based on mPEG-β-cyclodextrin and a camptothecin prodrug as drug release carriers[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(12): 941-955.

Figures/Tables 8

Table 1. Physicochemical properties of mPEG-β-CD/Ad-SS-CPT self-assembled micellesa.

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