A PH Responsive Complexation-based Drug Delivery System for Oxaliplatin

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2017 Oct 4

PMID 28970876

Citations 35

Authors

Bin Li

Zhao Meng

Qianqian Li

Xiayang Huang

Ziyao Kang

Huajin Dong

Junyi Chen

Ji Sun

Yansheng Dong

Jian Li

Xueshun Jia

Jonathan L Sessler

Qingbin Meng

Chunju Li

Affiliations

Soon will be listed here.

Abstract

A responsive drug delivery system (DDS) for oxaliplatin () has been designed with a view to overcoming several drawbacks associated with this anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability. The present approach is based on the direct host-guest encapsulation of by a pH-responsive receptor, carboxylatopillar[6]arene (). The binding affinities of for were found to be pH-sensitive at biologically relevant pH. For example, the association constant () at pH 7.4 [ = (1.02 ± 0.05) × 10 M] is 24 times larger than that at pH 5.4 [ = (4.21 ± 0.06) × 10 M]. Encapsulation of within the cavity did not affect its cytotoxicity as inferred from comparison studies carried out in several cancer cells (, the HepG-2, MCF-7, and A549 cell lines). On the other hand, complexation by serves to increase the inherent stability of in plasma by 2.8-fold over a 24 h incubation period. The formation of a ⊃ host-guest complex served to enhance in a statistically significant way the ability of to inhibit the regrowth of sarcoma 180 (S180) tumors in Kunming (KM) mice xenografts. The improved anticancer activity observed for ⊃ is attributed to the combined effects of enhanced stability of the host-guest complex and the pH-responsive release of . Specifically, it is proposed that is protected as the result of complex formation and then released effectively in the acidic tumor environment.

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