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Ni2+-mediated mitoxantrone encapsulation: improved efficacy of fast release formulation.

Abstract：

:Despite that in solution we cannot detect the interaction between Ni(2+) and mitoxantrone (MIT), Ni(2+) could mediate effective and stable MIT loading into large unilamellar vesicles (LUVs). The presence of nigericin had almost no influences on MIT encapsulation. However, in the presence of NH(3), the drug loading kinetics significantly altered. UV-vis spectrum analysis revealed that the absorption profile of liposomal MIT prepared with NiSO(4) gradient method was markedly different from that of liposomal MIT prepared with pH gradient method and that of free MIT. Three liposomal formulations were prepared, which were made from DMPC/chol, DPPC/chol and HSPC/chol and named LM-m, LM-p and LM-s. The in vitro release T(1/2) values for the formulations were 15.0, 28.2 and 38.5h, respectively. Following an intravenous injection into BDF1 mice at a dose of 4 mg/kg, the MIT plasma levels at 24h time point were 3.3, 11.3 and 12.7 microg/mL, considerably compared to that of free MIT group. In L1210 ascitic model, LM-m therapy resulted in approximately 60% long-term survivor (>60 days), and increased survival times in comparison with other treatments. However, both LM-p and LM-s formulations were less therapeutically active than free MIT. In conclusion, transmembrane NiSO(4) gradient could mediate effective MIT loading, and the formulation prepared with fluid lipid had fast release rate and improved efficacy in L1210 ascitic tumor model.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Cui J,Li C,Wang L,Wang C,Yang H,Li Y,Zhang L,Zhang L,Guo W,Liang M

doi

10.1016/j.ijpharm.2008.09.045

subject

Has Abstract

pub_date

2009-02-23 00:00:00

pages

24-30

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(08)00680-7

journal_volume

368

pub_type

杂志文章

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