Preparation of pH-Responsive Doxorubicin Nanocapsules by Combining High-gravity Antisolvent Precipitation with In-situ P
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doi: 10.1007/s40242-020-0007-4
Article
Preparation of pH-Responsive Doxorubicin Nanocapsules by Combining High-gravity Antisolvent Precipitation with In-situ Polymerization for Intracellular Anticancer Drug Delivery LIU Jie1, CHEN Bo2* and ZHANG Jianjun1* 1. College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China; 2. State Key Laboratory of NBC Protection for Civilian, Beijing 102205, P. R. China Abstract Owing to the low pH value in tumor and cancer cells, drug delivery systems based on pH-responsive polymer nanocarriers have been extensively explored for anticancer chemotherapy. Herein, we developed a pH-responsive doxorubicin(DOX) nanocapsule(named as DNanoCapsule) prepared by combining in-situ polymerization technique with high-gravity antisolvent precipitation technique through an amphiphilic polymerized surface ligand. DNanoCapsules show an obvious spherical core-shell structure with a single DOX nanoparticle encapsulated in the polymer layer. Dissolution rate studies prove that the DNanoCapsules have robust drug-release profiles under acidic environments due to the division of the pH-sensitive cross-linker, which triggers the collapse of the polymer layer. The in vitro investigations demonstrated that the DNanoCapsules exhibited high cellular uptake efficiency and cytotoxicity for both HeLa and MCF-7 cancer cells. Therefore, this work may provide a promising strategy to design and develop various stimuli-responsive drug nanocapsules for the treatment of cancer or other diseases. Keywords pH-Responsive; Nanocapsule; In-situ polymerization; High-gravity antisolvent precipitation; Anticancer chemotherapy
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Introduction
tedious separation of unconjugated polymer from the products effectively[14]. Recently, high-gravity antisolvent precipitation(HGAP) in a rotating packed bed has been utilized for preparing drug nanoparticles[15―18]. Owing to the intensified mass transfer and micromixing effect under high gravity, the drug nucleation amounts and rates can be increased greatly, leading to the formation of drug nanoparticles with a smaller size, uniform size distribution, low crystallinity, and high dissolution rate[19]. The drug nanoparticles can be modified further by introducing a surface ligand containing various active groups in HGAP, to achieve desirable functions. Over the past several decades, a wide variety of stimuli-responsive factors have been utilized to design smart polymer nanocarriers for anticancer drug delivery[20―24]. Specifically, by taking advantage of the acidic microenvironment of tumor and cancer cells, polymer nanocarriers with acidsensitive bonds, whose cleavage enables the rapid release of the loading drugs, have been extensively developed[25―28]. Herein, we developed a pH-responsive DOX nanocapsule(DNanoCapsule) with a high DLC via a simple method, in which both the HGAP and in-situ polymerization techniques are employed using an amphiphilic polymerized surface ligand.
Nanotechnology has revolutionized the fabrication of drug delivery
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