National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing , P.R. China .
Drug Dev Ind Pharm. 2014 Feb;40(2):244-51. doi: 10.3109/03639045.2012.756009. Epub 2013 Apr 19.
The objective of this study is to test the hypothesis that the phase transition temperature (T(m)), the main property of liposomes, can be easily controlled by changing the molar ratio of hydrogenated soy phosphatidylcholine (HSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC) after drug encapsulation.
Brucine, an antitumor alkaloid, was encapsulated into the liposomes with different HSPC/DPPC compositions. The T(m)s of the brucine-loaded liposomes (BLs) were determined by differential scanning calorimetry (DSC). Then the physicochemical properties and pharmacokinetics of the BLs with different HSPC/DPPC compositions were investigated and compared.
The results of DSC revealed that HSPC and DPPC can combine into one phase. The findings of molecular modeling study suggested that HSPC interacts with DPPC via electrostatic interaction. The molar ratio of HSPC/DPPC influenced the sizes of BLs but had little effect on the entrapment efficiency (EE). The stability of BLs was improved with the increase of the HSPC ratios, especially with the presence of plasma. Following i.v. administration, it was found that AUC values of BLs in vivo were directly related to the HSPC/DPPC ratios of BLs, namely the T(m)s of BLs.
The behavior of liposomes, especially in vivo pharmacokinetic behavior, can be controlled by the modification of T(m).
The characterization of BLs in vitro and in vivo had demonstrated that the Tm could be flexibly modified for liposomes composed of both HSPC and DPPC. Using HSPC/DPPC composition may be an efficient strategy to control the T(m), thus control the in vivo pharmacokinetic behavior, of BLs.
本研究旨在验证以下假设，即通过改变氢化大豆磷脂酰胆碱（HSPC）和 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱（DPPC）的摩尔比，在药物包封后，可以轻松控制脂质体的相变温度（T(m)），这是脂质体的主要特性。
将布藜芦碱（一种抗肿瘤生物碱）包封到具有不同 HSPC/DPPC 组成的脂质体中。通过差示扫描量热法（DSC）测定载布藜芦碱脂质体（BLs）的 T(m)。然后，研究并比较了具有不同 HSPC/DPPC 组成的 BLs 的理化性质和药代动力学。
DSC 结果表明，HSPC 和 DPPC 可以结合成一个相。分子建模研究的结果表明，HSPC 通过静电相互作用与 DPPC 相互作用。HSPC/DPPC 的摩尔比对 BLs 的粒径有影响，但对包封效率（EE）影响较小。HSPC 比例的增加提高了 BLs 的稳定性，尤其是在存在血浆的情况下。静脉注射给药后发现，BLs 的体内 AUC 值与 BLs 的 HSPC/DPPC 比值直接相关，即 BLs 的 T(m)。
脂质体的行为，特别是体内药代动力学行为，可以通过 T(m)的修饰来控制。
BLs 的体外和体内特性表明，Tm 可以灵活地修饰由 HSPC 和 DPPC 组成的脂质体。使用 HSPC/DPPC 组成可能是控制 T(m)的有效策略，从而控制 BLs 的体内药代动力学行为。
