Harashima H, Ochi Y, Kiwada H
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Biopharm Drug Dispos. 1994 Apr;15(3):217-25. doi: 10.1002/bdd.2510150304.
The purpose of this study is to propose a new method for quantitative evaluation of liposome degradation in serum. The time course of liposome degradation in rat serum was monitored continuously, using 6(5)-carboxyfluorescein as an aqueous phase marker. The degradation curves exhibited three characteristic phases: lag time, degradation, and plateau. This curve was described by a kinetic model with three parameters: lag time (tau), first-order degradation rate constant (k), and maximum degradation (alpha). The rate and extent of the degradation of liposomes were evaluated separately in terms of k and alpha, respectively. The effects of size and concentration of liposomes on their degradation kinetics were examined using this method. Both k and alpha increased with increasing liposomal size. The increased affinity of larger liposomes for complement was suggested to increase both k and alpha. On the other hand, alpha decreased with increasing liposomal concentration without altering k. The decreased extent of degradation was considered to result from the depletion of complement components. There was no significant effect of size and concentration of liposomes on tau. Quantitative evaluation of the rate and extent of degradation of liposomes will provide deeper insights into the interaction between liposomes and serum components, and basic information on liposomes as potential drug carriers.
本研究的目的是提出一种定量评估血清中脂质体降解的新方法。以6(5)-羧基荧光素作为水相标记物，连续监测大鼠血清中脂质体的降解时间进程。降解曲线呈现出三个特征阶段：延迟期、降解期和平稳期。该曲线由一个具有三个参数的动力学模型描述：延迟时间（τ）、一级降解速率常数（k）和最大降解量（α）。脂质体降解的速率和程度分别根据k和α进行评估。使用该方法研究了脂质体大小和浓度对其降解动力学的影响。k和α均随脂质体大小的增加而增加。较大脂质体对补体的亲和力增加被认为会导致k和α均升高。另一方面，α随脂质体浓度的增加而降低，而k不变。降解程度的降低被认为是补体成分耗竭的结果。脂质体的大小和浓度对τ没有显著影响。对脂质体降解速率和程度的定量评估将为深入了解脂质体与血清成分之间的相互作用以及脂质体作为潜在药物载体的基本信息提供帮助。
