Molecularly imprinted layer-coated hollow polysaccharide microcapsules toward gate-controlled release of water-soluble drugs

Abstract

Molecularly imprinted polymers (MIPs) as drug delivery carriers have been explored, but it still remains a significant challenge to achieve a high drug loading amount and controlled drug release rate of MIPs. Here, we report a layer-by-layer self-assembly method for doxorubicin (DOX) imprinting of biocompatible microcapsules, which consist of carboxymethyl cellulose–(chitosan/alginate)₅ and are able to encapsulate and deliver DOX. It has been demonstrated that the maximum loading capacity of the obtained hollow molecularly imprinted microcapsules (MIMs) to DOX was up to 155.1 μmol g⁻¹. Uncommonly, the release process of DOX-loaded MIMs could be sustained for more than 168 h, resulting from the imprinted sites being blocked by DOX molecules, which entered the imprinted sites through electrostatic interaction. Moreover, the interaction could be weakened at lower pH due to the protonation of the carboxyl groups of O-carboxymethyl chitosan, leading to the DOX departing from the imprinted sites (namely DOX release). Meanwhile, in vitro experiments demonstrated that the hollow DOX-imprinted microcapsules had good biocompatibility, the encapsulated DOX could effectively induce the apoptosis of U373 malignant glioma cells and had better efficacy than that of free DOX in terms of tumor inhibition within 144 h. These findings indicate that the construction of the novel smart microcapsules of natural polymers plays a crucial role in the performance of controlled drug release. This facile strategy reported herein can be further expected to fabricate delivery systems of various water-soluble drugs.