期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 40, 期 2, 页码 244-251出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/03639045.2012.756009
关键词
Brucine; liposomes; molecular modeling; pharmacokinetics; phase transition temperature; phosphatidylcholine
资金
- Open Project Program of National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine [2011ZYX3-003]
- National Nature Science Foundation of China [30701111, 81001644]
- Guangdong Nature Science Foundation [10451040701004643]
Objective: 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. Materials and methods: 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. Results: 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. Discussion: The behavior of liposomes, especially in vivo pharmacokinetic behavior, can be controlled by the modification of T-m. Conclusion: The characterization of BLs in vitro and in vivo had demonstrated that the T-m 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 behavio, of BLs.
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