Exploratory Pharmaceutical Development, Merck KGaA, Frankfurter Straße 250, 64293, Darmstadt, Germany.
Pharm Res. 2012 Feb;29(2):448-59. doi: 10.1007/s11095-011-0555-x. Epub 2011 Aug 31.
Stability of polymeric micelles upon injection is essential for a drug delivery system but is not fully understood. We optimized an analytical test allowing quantification of micellar stability in biofluids and applied it to a variety of block copolymer micelles with different hydrophobic block architechtures.
Polymeric micelles were prepared from four different polymers and investigated via encapsulation of two fluorescent dyes. Samples were incubated in human serum; changes in Foerster Resonance Energy Transfer (FRET) were recorded as a function of time. This fluorescence-based approach was supported semi-quantitatively by results from Asymmetrical Flow Field-Flow-Fractionation (AF4).
After incubation experiments, micellar stability was determined by calculation of two stability-indicating parameters: residual micellar fractions (RMFs) and in vitro serum half-lives. Both parameters showed that PEG-PVPy micelles rapidly destabilized after 3 h (RMF < 45%), whereas PEG-PLA, PEG-PLGA and PEG-PCL micelles were far more stable (RMFs 65 to 98%).
This FRET-based assay is a valuable tool in evaluating and screening serum stability of polymeric micelles and revealed low serum stability of PEG-PVPy micelles compared to polyester-based micelles.
对于药物传递系统而言，聚合物胶束在注射后的稳定性至关重要，但目前人们对此尚未充分了解。我们优化了一种分析测试方法，该方法可定量评估生物流体中胶束的稳定性，并将其应用于具有不同疏水嵌段结构的多种嵌段共聚物胶束。
用四种不同的聚合物制备聚合物胶束，并通过两种荧光染料的包封进行研究。将样品在人血清中孵育；随时间变化记录Förster 共振能量转移（FRET）的变化。该荧光法通过不对称流场流分离（AF4）的结果得到半定量支持。
孵育实验后，通过计算两个稳定性指示参数来确定胶束稳定性：残余胶束分数（RMF）和体外血清半衰期。这两个参数均表明，PEG-PVPy 胶束在 3 小时后迅速失稳（RMF<45%），而 PEG-PLA、PEG-PLGA 和 PEG-PCL 胶束则稳定得多（RMF 为 65%至 98%）。
该基于 FRET 的测定法是评估和筛选聚合物胶束血清稳定性的有效工具，与聚酯基胶束相比，PEG-PVPy 胶束的血清稳定性较低。
