Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tiss...Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.展开更多
文摘Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.
