Viroonchatapan E, Ueno M, Sato H, Adachi I, Nagae H, Tazawa K, Horikoshi I
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Japan.
Pharm Res. 1995 Aug;12(8):1176-83. doi: 10.1023/a:1016216011016.
Dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), were prepared and characterized in order to investigate their possibility for magnetic drug targeting.
TMs containing calcein were prepared at various DM concentrations by reverse-phase evaporation of dipalmitoylphosphatidylcholine (DPPC). They were evaluated for their physicochemical properties including size, DM capture, magnetite distribution within liposomes, and temperature-dependent calcein release. Moreover, a novel on-line flow apparatus with a sample injector, a coil of tubing placed in an electromagnet, and a fluorescence detector was developed for quantifying the magnetic responsiveness of TMs. This device allowed us a real-time measurement of percentage holding of TMs by magnetic field.
Due to water-soluble property of DM, higher contents of magnetite up to 490 mg per mmol DPPC were successfully incorporated into the liposomes with DM than with conventional magnetite (Fe3O4). Thermosensitivity and lipid integrity of TMs were not influenced by inclusion of DM. Using the on-line flow system, percentage holding of TMs by magnetic field was shown to vary with several factors; it increases as the magnetic field strength increases, the fluid flow rate decreases, the magnetite content increases, and the liposome concentration increases. Typically, at 490 mg incorporated magnetite per mmol DPPC, 0.5 ml/min-fluid flow rate, and high magnetic field strength (> or = 10 kiloGauss), approximately 100% of TMs were found to be held.
The TMs were suggested to be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.
制备并表征了包载葡聚糖磁铁矿（DM）的热敏脂质体，即热敏磁性脂质体（TMs），以研究其用于磁性药物靶向的可能性。
通过二棕榈酰磷脂酰胆碱（DPPC）的反相蒸发法，在不同DM浓度下制备了包载钙黄绿素的TMs。对其理化性质进行了评估，包括粒径、DM包封率、磁铁矿在脂质体内的分布以及温度依赖性钙黄绿素释放。此外，开发了一种新型在线流动装置，该装置带有进样器、置于电磁铁中的盘管以及荧光检测器，用于定量TMs的磁响应性。该装置使我们能够实时测量磁场对TMs的捕获百分比。
由于DM的水溶性，与传统磁铁矿（Fe3O4）相比，高达每毫摩尔DPPC 490毫克的更高含量磁铁矿成功地被包载到含DM的脂质体中。DM的加入并未影响TMs的热敏性和脂质完整性。使用在线流动系统，结果表明磁场对TMs的捕获百分比受多种因素影响；它随磁场强度增加、流体流速降低、磁铁矿含量增加和脂质体浓度增加而增加。通常，在每毫摩尔DPPC包载490毫克磁铁矿、流体流速为0.5毫升/分钟以及高磁场强度（≥10千高斯）时，发现约100%的TMs被捕获。
TMs被认为在未来通过磁性靶向结合热疗响应性药物释放用于癌症治疗方面具有应用价值。
