Le Dévédec Frantz, Houdaihed Loujin, Allen Christine
Leslie Dan Faculty of Pharmacy, University of Toronto;
Leslie Dan Faculty of Pharmacy, University of Toronto.
J Vis Exp. 2016 Oct 10(116):54422. doi: 10.3791/54422.
In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE). Characterization of the copolymer revealed a narrow molecular distribution (PDI < 1.03) and confirmed the degree of polymerization of mPEG122-b-(PheGE)15. The critical micelle concentration of the copolymer was evaluated using an established fluorescence method with the aggregation behavior evaluated by dynamic light scattering and transmission electronic microscopy. The potential of the copolymer for use in drug delivery applications was evaluated in a preliminary manner including in vitro biocompatibility, loading and release of the hydrophobic anti-cancer drug doxorubicin (DOX). A stable micelle formulation of DOX was prepared with drug loading levels up to 14% (wt%), drug loading efficiencies > 60% (w/w) and sustained release of drug over 4 days under physiologically relevant conditions (acidic and neutral pH, presence of albumin). The high drug loading level and sustained release is attributed to stabilizing π-π interactions between DOX and the core-forming block of the micelles.
在本研究中，通过在甲氧基聚乙二醇（mPEG-b-PPheGE）上进行苯基缩水甘油醚（PheGE）的活性阴离子聚合反应，合成了一种包含带有苯基的成核嵌段的两亲共聚物。对该共聚物的表征显示其具有较窄的分子分布（PDI < 1.03），并确定了mPEG122-b-(PheGE)15的聚合度。使用既定的荧光方法评估了该共聚物的临界胶束浓度，并通过动态光散射和透射电子显微镜对其聚集行为进行了评估。以初步方式评估了该共聚物在药物递送应用中的潜力，包括体外生物相容性、疏水性抗癌药物阿霉素（DOX）的负载和释放。制备了一种稳定的DOX胶束制剂，其载药量高达14%（重量），载药效率> 60%（w/w），并且在生理相关条件（酸性和中性pH值、存在白蛋白）下药物可持续释放4天。高载药量和持续释放归因于DOX与胶束的成核嵌段之间稳定的π-π相互作用。
