Delivery of doxorubicin and paclitaxel from double-layered microparticles: The effects of layer thickness and dual-drug vs. single-drug loading
Delivery of doxorubicin and paclitaxel from double-layered microparticles: The effects of layer thickness and dual-drug vs. single-drug loading
复制标题
DOI：
10.1016/j.actbio.2015.08.051
复制
发表时间：
2015-11-01
影响因子：
9.7
通讯作者：
Loo, Say Chye Joachim
中科院分区：
文献类型：
--
作者：
Lee, Wei Li;Guo, Wei Mei;Loo, Say Chye Joachim
采用溶剂蒸发技术将聚（D， l -乳酸-羟基乙酸，50:50）（PLGA）和聚（l -乳酸）（PLLA）组成的双层微颗粒分别装上盐酸阿霉素（DOX）和紫杉醇（PCTX）。DOX定位在PLGA外壳中，PCTX定位在PLLA核心中。本研究的目的是探讨改变双药、双层微颗粒的层厚如何影响药物释放动力学及其抗肿瘤能力，以及对单药微颗粒的抗肿瘤能力。与双药微粒子相比，载PCTX的双层微粒子具有更致密的外壳，延迟了PCTX的初始释放。从DOX负载和双重药物负载的微颗粒中观察到与初始爆发相似的DOX释放。通过特定的层厚度定制，可以在2个月内抑制DOX的初始爆发和两种药物的持续共同递送。利用MCF-7细胞球体的活力研究表明，双重载药的双层微颗粒控制PCTX和DOX的共同递送可以更好地降低球体的生长速度。这项研究为如何通过调整双层微颗粒的层厚度来控制两种药物的释放动力学以及如何共同递送可能获得更好的抗癌效果提供了机制见解。虽然有报道称多种药物的释放可以成功实现细胞凋亡并最大限度地减少耐药性，但大多数传统的颗粒系统一次只能递送一种药物。最近，尽管许多制剂（如胶束纳米颗粒、脂质体）已经成功地递送了两种或两种以上的抗癌药物，但由于复杂的药物装载过程和亲水性药物的快速释放，这些药物的持续共递送仍然不足。因此，目前的工作报告了多层颗粒系统，它同时承载不同的药物，同时能够在几个月内调整它们的个别释放。我们相信我们的发现会引起《生物材料学报》读者的兴趣，因为所提出的系统可以为如何通过速率控制载体释放两种药物以进行联合化疗开辟新的途径。(C) 2015材料学报Elsevier Ltd.出版。版权所有。
Double-layered microparticles composed of poly(D,L-lactic-co-glycolic acid, 50:50) (PLGA) and poly(L-lactic acid) (PLLA) were loaded with doxorubicin HCl (DOX) and paclitaxel (PCTX) through a solvent evaporation technique. DOX was localized in the PLGA shell, while PCTX was localized in the PLLA core. The aim of this study was to investigate how altering layer thickness of dual-drug, double-layered microparticles can influence drug release kinetics and their antitumor capabilities, and against single-drug microparticles. PCTX-loaded double-layered microparticles with denser shells retarded the initial release of PCTX, as compared with dual-drug-loaded microparticles. The DOX release from both DOX-loaded and dual-drug-loaded microparticles were observed to be similar with an initial burst. Through specific tailoring of layer thicknesses, a suppressed initial burst of DOX and a sustained co-delivery of two drugs can be achieved over 2 months. Viability studies using spheroids of MCF-7 cells showed that controlled co-delivery of PCTX and DOX from dual-drug-loaded double-layered microparticles were better in reducing spheroid growth rate. This study provides mechanistic insights into how by tuning the layer thickness of double-layered microparticles the release kinetics of two drugs can be controlled, and how co-delivery can potentially achieve better anticancer effects.Statement of SignificanceWhile the release of multiple drugs has been reported to achieve successful apoptosis and minimize drug resistance, most conventional particulate systems can only deliver a single drug at a time. Recently, although a number of formulations (e.g. micellar nanoparticles, liposomes) have been successful in delivering two or more anticancer agents, sustained co-delivery of these agents remains inadequate due to the complex agent loading processes and rapid release of hydrophilic agents. Therefore, the present work reports the multilayered particulate system that simultaneously hosts different drugs, while being able to tune their individual release over months. We believe that our findings would be of interest to the readers of Acta Biomaterialia because the proposed system could open a new avenue on how two drugs can be released, through rate-controlling carriers, for combination chemotherapy. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.