Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation.
Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation.
复制标题
基于树突状纳米粒子的药物输送系统，用于增强膀胱内滴注。
DOI：
10.2147/ijn.s140111
复制
发表时间：
2017
影响因子：
8
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Qiu X;Cao K;Lin T;Chen W;Yuan A;Wu J;Hu Y;Guo H
经尿道膀胱肿瘤切除术后膀胱内灌注抗肿瘤药物是治疗浅表性膀胱癌的标准策略。然而，目前膀胱内灌注的疗效是有限的，部分原因是尿道的渗透性差。因此，我们的目的是开发一种高渗透性，靶向释放药物传递系统，以提高膀胱灌注的疗效。将PAMAM与聚乙二醇（PEG）偶联，形成PEG-PAMAM复合物作为纳米载体。然后将多柔比星（DOX）包封到PEG-PAMAM中以产生负载DOX的PEG-PAMAM纳米颗粒（PEG-PAMAM-DOX）。结果表明，PEG-PAMAM是一种稳定的纳米载体，粒径小，生物安全性好。DOX从PEG-PAMAM-DOX的释放是缓慢的，但在酸性微环境（pH =5.0）中可以有效地触发。作为药物载体，PEG-PAMAM能有效地渗透小鼠膀胱尿道，膀胱灌注后增加膀胱壁内DOX的量。使用小鼠原位膀胱癌模型评价PEG-PAMAM-DOX的抗肿瘤作用。与游离DOX相比，PEG-PAMAM-DOX显示出用于膀胱内滴注的DOX的显著改善的功效，且副作用有限。总之，我们成功地开发了一种基于PEG-PAMAM的药物传递系统，以增强膀胱灌注的抗肿瘤作用。
Intravesical instillation of antitumor agents following transurethral resection of bladder tumors is the standard strategy for the treatment of superficial bladder cancers. However, the efficacy of current intravesical instillation is limited partly due to the poor permeability of the urothelium. We therefore aimed to develop a high-penetrating, target-releasing drug delivery system to improve the efficacy of intravesical instillation. PAMAM, a dendrimer, were conjugated with polyethylene glycol (PEG) to form PEG-PAMAM complex as a nanocarrier. Doxorubicin (DOX) was then encapsulated into PEG-PAMAM to generate DOX-loaded PEG-PAMAM nanoparticles (PEG-PAMAM-DOX). Our results indicated that the PEG-PAMAM was a stable nanocarrier with small size and great biosafety. The release of DOX from PEG-PAMAM-DOX was sluggish but could be effectively triggered in an acid microenvironment (pH =5.0). As a drug carrier, PEG-PAMAM could penetrate mice bladder urothelium effectively and increase the amount of DOX within the bladder wall after intravesical instillation. The antitumor effect of PEG-PAMAM-DOX was evaluated using an orthotopic bladder cancer model in mice. Compared to free DOX, PEG-PAMAM-DOX showed significantly improved efficacy of DOX for intravesical instillation with limited side effects. In conclusion, we successfully developed a PEG-PAMAM-based drug delivery system to enhance the antitumor effect of intravesical instillation.