Application of Asymmetrical Flow Field-Flow Fractionation for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles.

Application of Asymmetrical Flow Field-Flow Fractionation for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles.
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DOI:
10.3390/ijms221910456
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发表时间:
2021-09-28
影响因子:
5.6
通讯作者:
Brandl M
Brandl M
中科院分区:
生物学2区
文献类型:
--
作者:
Skupin-Mrugalska P;Elvang PA;Brandl M

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脂质体的大小和活性物质的体外释放属于脂质体载体的关键质量属性。在这里,我们应用不对称流场-流动分馏(AF4)技术来表征由薄膜水化/挤压或微流控法制备的针状脂质体。囊泡的大小是从分馏后的多角度激光光散射(AF4)得出的,并与动态光散射测量得出的大小进行了比较。此外,我们采用了一种先前开发的AF4方法来研究锌酞菁(ZnPc)从透气脂质体中的释放/转移。为此,将酒精性脂质体与作为接收器(模拟生物汇)的大受体脂质体孵育,然后用AF4进行分离。在孵育过程中,ZnPc从供体转移到受体组分,直到达到平衡。该过程遵循一级动力学,半衰期为119.5-277.3分钟,具体取决于配方。释放机制被认为代表了Fickian扩散和脂质体松弛的组合。转移速率常数与脂质体的大小成正比,与ZnPc/POPC的摩尔比成反比。我们的结果证实了基于AF4的方法在体外研究亲脂性有效载荷的释放/转移的有效性,这可能有助于估计药物在体内从脂质体载体中的有害损失。
Liposome size and in vitro release of the active substance belong to critical quality attributes of liposomal carriers. Here, we apply asymmetric flow field-flow fractionation (AF4) to characterize theranostic liposomes prepared by thin lipid film hydration/extrusion or microfluidics. The vesicles’ size was derived from multi-angle laser light scattering following fractionation (AF4) and compared to sizes derived from dynamic light scattering measurements. Additionally, we adapted a previously developed AF4 method to study zinc phthalocyanine (ZnPc) release/transfer from theranostic liposomes. To this end, theranostic liposomes were incubated with large acceptor liposomes serving as a sink (mimicking biological sinks) and were subsequently separated by AF4. During incubation, ZnPc was transferred from donor to acceptor fraction until reaching equilibrium. The process followed first-order kinetics with half-lives between 119.5–277.3 min, depending on the formulation. The release mechanism was postulated to represent a combination of Fickian diffusion and liposome relaxation. The rate constant of the transfer was proportional to the liposome size and inversely proportional to the ZnPc/POPC molar ratio. Our results confirm the usefulness of AF4 based method to study in vitro release/transfer of lipophilic payload, which may be useful to estimate the unwanted loss of drug from the liposomal carrier in vivo.
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