Brucine-loaded liposomes composed of HSPC and DPPC at different ratios: in vitro and in vivo evaluation.

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 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.

[Study on preparation and thermosensitive release property of composite phospholipid liposomes containing total alkaloids from Strychnos nux-vomica].

To prepare composite phospholipid liposomes containing total alkaloids of Strychnos nux-vomica with hydrogenated soybean phosphatidylcholine (HSPC) and 1, 2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC), and compare with normal DPPC thermosensitive liposomes for thermosensitive release property. Total alkaloids were extracted from S. nux-vomica with the impregnation method and further purified. Liposomes containing total alkaloids, thermosensitive liposomes and conventional thermosensitive liposomes without thermosensitive release property were prepared by ammonium sulfate transmembrane gradients and stealth liposome technique. Their encapsulation efficiency (EE), grain size, zeta potential and drug release behavior were compared. Their EEs and zeta potentials were almost identical; but the grain sizes of composite phospholipid liposomes and thermosensitive liposomes were significantly smaller than conventional liposomes. After comparing release behaviors of the three liposomes at 37, 43 degrees C, we found that the release of composite phospholipid liposomes was significantly lower than that of thermosensitive liposomes at 37 degrees C, but higher than that of thermosensitive liposomes at 43 degrees C. Meanwhile, conventional liposomes, with a very high phase-transition temperature, showed only slight release behavior at both temperatures. The study results showed that composite phospholipid liposomes had a better thermosensitive release behavior when the dosage of lysophosphatidic was reduced by 2. 5 times.

Thermosensitive liposomes with higher phase transition temperature for targeted drug delivery to tumor.

Thermosensitive liposomes (TSL) in combination with local hyperthermia (HT) represent a promising tool for tumor specific drug delivery. The objective of the study was to investigate the influence of phase transition temperature (Tm) on the properties of TSL. High temperature triggered TSL (HTSL), low temperature triggered TSL (LTSL) and non-TSL (NTSL) were prepared and temperature sensitive release properties were extensively compared in different media. Mouse plasma was determined to have similar effect on the release profiles compared to human plasma, in which complete release were obtained at 38 °C and 40 °C for LTSL and HTSL, respectively. The temperature at which complete release achieved was found to be obviously lower than Tm. Brucine, an antitumor alkaloid, was encapsulated into different TSLs. After HT treatment, the viabilities of SMMC 7721 cells were determined to be 21.3±3.8% and 16.8±3.3% for 127 µM brucine LTSL and HTSL, respectively. Treating the tumor-bearing mice with LTSL, HTSL and NTSL led to significantly increased brucine uptake in the heated tumor site compared to the brucine solution group by 2.30, 3.80 and 2.26-fold, respectively. The results of this study suggested that Tm of TSL should be increased to obtain improved drug delivery efficiency to tumor.