標題: In situ DOX-calcium phosphate mineralized CPT-amphiphilic gelatin nanoparticle for intracellular controlled sequential release of multiple drugs
作者: Li, Wei-Ming
Su, Chia-Wei
Chen, Yu-Wei
Chen, San-Yuan
材料科學與工程學系
Department of Materials Science and Engineering
關鍵字: Calcium phosphate;pH-sensitivity;Drug release;Amphiphilic gelatin;Multidrug resistance
公開日期: 15-Mar-2015
摘要: A co-delivery strategy has been developed to achieve the synergistic effect of a hydrophobic drug (camptothecin, CPT) and a hydrophilic drug (doxorubicin, DOX) by utilizing the unique structure of amphiphilic gelatin/camptothecin @calcium phosphate-doxorubicin (AG/CPT@CaP-DOX) nanoparticles as a carriers in order to replace double emulsions while preserving the advantages of inorganic materials. The hydrophobic agent (CPT) was encapsulated via emulsion with an amphiphilic gelatin core, and subsequently mineralized by CaP-hydrophilic drug (DOX) through precipitation to form a CaP shell on the CPT-AG amphiphilic gelatin core so that drug molecules with different characteristics (i.e. hydrophobic and hydrophilic) can be encapsulated in different regions to avoid their interaction. The existence of the CaP shell can protect the DOX against free release and cause an increased transfer of DOX across membranes, overcoming multidrug resistance. Release studies from core-shell carriers showed the possibility of achieving sequential release of more than one type of drug by controlling the pH-sensitive CaP shell and degradable AG core. The highly pH-responsive behavior of the carrier can modulate the dual-drug-release of DOX/CPT, specifically in acidic intracellular pH environments. The AG/CPT@CaP-DOX nanoparticles also exhibited higher drug efficiencies against MCF-7/ADR cells than MCF-7 cells, thanks to a synergistic cell cycle arrest/apoptosis-inducing effect between CPT and DOX. As such, this core shell system can serve as a general platform for the localized, controlled, sequential delivery of multiple drugs to treat several diseases, especially for multidrug-resistant cancer cells. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
URI: http://dx.doi.org/10.1016/j.actbio.2014.12.013
http://hdl.handle.net/11536/124508
ISSN: 1742-7061
DOI: 10.1016/j.actbio.2014.12.013
期刊: ACTA BIOMATERIALIA
Volume: 15
起始頁: 191
結束頁: 199
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