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MAGNETIC TARGETING OF THERMOSENSITIVE MAGNETOLIPOSOMES TO MOUSE LIVERS IN AN IN SITU ON-LINE PERFUSION SYSTEM

机译:原位在线灌注系统中热敏磁脂质体对小鼠肝脏的磁性靶向

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We recently reported the preparation and in vitro targeting of dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magneto-liposomes (TMs) [Viroonchatapan et al., Pharm. Res. 12 1176-1183 (1995)]. The current study was designed to determine whether these novel liposomes can be targeted to the mouse liver with the aid of an extracorporeal magnet. An on-line liver perfusion system consisting primarily of a sample injector, permanent magnets, and a fluorescence detector was established for a real-time measurement of targeting efficiency of TMs containing calcein as a fluorescent marker. Normal and reticuloendothelial system (RES)-blocked livers from mice were used for the perfusion experiments. In the RES-blocked livers, percentage holdings of TMs were 73-80% and 26-45% in the presence and absence of magnetic field, respectively, indicating an efficient targeting of TMs with a targeting advantage index (TAI) of 1.6-3.1. On the other hand, TAI in the normal livers was found to be 1.1-1.4 and less than that in the RES-blocked livers, suggesting a role of RES uptake of TMs. The effects of DM concentrations in TM suspensions on the percentage holding of TMs were shown to be minor. Liposome concentration dependence was observed for hepatic uptake of TMs, possibly because of the saturation of phagocytosis by Kupffer cells. The present results suggest that TMs would be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia. [References: 38]
机译:我们最近报道了掺有葡聚糖磁铁矿(DM)的热敏脂质体,即热敏磁性脂质体(TM)的制备和体外靶向[Viroonchatapan等人,Pharm.Sci。,Vol.5,pp.5(1)]。 Res。 12 1176-1183(1995)]。当前的研究旨在确定借助体外磁体能否将这些新型脂质体靶向小鼠肝脏。建立了一个主要由样品注射器,永磁体和荧光检测器组成的在线肝脏灌注系统,用于实时测量含有钙黄绿素作为荧光标记物的TM的靶向效率。小鼠的正常和网状内皮系统(RES)阻断的肝脏用于灌注实验。在受RES阻滞的肝脏中,在有磁场和无磁场的情况下,TM的持股率分别为73-80%和26-45%,这表明TM的有效靶定具有1.6-3.1的靶向优势指数(TAI) 。另一方面,正常肝脏中的TAI被发现为1.1-1.4,低于RES阻断肝脏中的TAI,这表明RES吸收TM的作用。结果表明,TM悬浮液中DM浓度对TM保持百分数的影响很小。脂质体浓度依赖于肝脏对TMs的摄取,这可能是由于库普弗细胞吞噬作用的饱和所致。目前的结果表明,通过磁靶向结合对热疗反应的药物释放,TMs在未来的癌症治疗中将是有用的。 [参考:38]

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