Poly(2‐oxazoline) block copolymer based formulations of taxanes: effect of copolymer and drug structure, concentration, and environmental factors

共聚物 材料科学 胶束 聚合物 恶唑啉 两亲性 化学工程 高分子化学 水溶液 有机化学 化学 复合材料 工程类 催化作用
作者
Youngee Seo,Anita Schulz,Yingchao Han,Zhijian He,Herdis Bludau,Xiaomeng Wan,Jing Tong,Tatiana K. Bronich,Marina Sokolsky‐Papkov,Robert Luxenhofer,Rainer Jordan,Alexander V. Kabanov
出处
期刊:Polymers for Advanced Technologies [Wiley]
卷期号:26 (7): 837-850 被引量:63
标识
DOI:10.1002/pat.3556
摘要

Many current nanoformulations of taxanes are hampered by low drug‐loading capacity and unfavorable physicochemical characteristics such as large particles size (>100 nm) and/or low size uniformity. We have previously reported on taxane nanoformulations, based on poly(2‐oxazoline) polymeric micelles that display an extremely high taxane loading capacity (>40% w/w) and particle size below 50 nm. Previous work was based on a triblock copolymer having poly(2‐butyl‐2‐oxazoline) as the hydrophobic block and poly(2‐methyl‐2‐oxazoline) as the hydrophilic blocks. This paper explores the effects of various formulation parameters such as (i) the drug and polymer structure; (ii) the drug and polymer concentration; and (iii) the composition of aqueous medium on the solubilization behavior and physicochemical properties of the resulting formulations. In addition, in vitro anticancer activity is reported. Despite numerous variations of the hydrophobicity, polarity or addition of aromatic residues in the hydrophobic core, the triblock copolymer with the poly(2‐butyl‐2‐oxazoline) block remains the polymer with the highest drug‐loading capacity. Notably, the formulation was easily scalable with uncompromised encapsulation efficacy, loading capacity, and physicochemical properties. The taxane formulations were stable upon storage (water, saline, and dextrose solution) for 1–2 weeks and could be lyophilized and re‐dispersed without compromising the formulation properties. Furthermore, the micelles remained stable upon dilution. The drug‐loaded poly(2‐oxazoline) micelles showed high toxicity against several cancer cell lines. Taken together, these results underscore the potential of poly(2‐oxazoline) micelles as formulation excipient for taxanes and possibly other hydrophobic drugs. Copyright © 2015 John Wiley & Sons, Ltd.
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