Functional Liposomal Membranes for Triggered Release
Functional Liposomal Membranes for Triggered Release
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DOI：
10.1007/978-1-60327-360-2_16
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发表时间：
2010-01-01
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影响因子：
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通讯作者：
Kocer, Armagan
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文献类型：
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作者：
Kocer, Armagan
在发现脂质体后不久(J Mol Biol 13：238-252,1965)，Gregoriadis等人。(《柳叶刀》1：1313-1316,1974)建议将其用作药物输送囊泡。从那时起，在脂质体组成、有效的药物包封率和保留率、稳定性和靶向性方面取得了许多进展(Biochim BiPhys Acta 1113：171-199,1992)。然而，尽管脂质体中的一些非常有效的药物制剂已被临床批准，但在大多数情况下，从这种理想的、长循环的、空间稳定的脂质体中被动释放的药物量不足以显示出治疗效果(癌症化学药物化学49：201-210,2002；癌症化学药物化学48：266-268,2001；EUJ癌症37：2015-2022,2001；乳腺癌治疗77：185-188,2003；肺癌34：427-432,2001；癌症化学其他药物化学50：131-136,2002)。已经假设在靶部位的增强释放将显著提高脂质体药物的特异性和有效性(J Liposome Res 8：299-335,1998；Pharmaco Rev 51：691-744,1999；Curt Opin Mol Ther 3：153-158,2001)。为了解决这一挑战，更多的研究努力指向触发释放，以回应目标部位的特定刺激。在这里，我们提出了一种工程设计的细菌通道蛋白，作为空间稳定脂质体中的遥控纳阀，在命令下触发脂质体内容物的释放。
Shortly after the discovery of liposomes (J Mol Biol 13:238-252, 1965), Gregoriadis et al. (Lancet 1:1313-1316, 1974) Suggested their use as drug delivery vesicles. Since then there have been many developments in liposomal composition, efficient drug encapsulation and retention, stability, and targeting(Biochim Biophys Acta 1113:171-199, 1992). However,even though some of the very potent drug formulations in liposomes were clinically approved, in most cases the amount of drug passively released from Such ideal, long-circulating, sterically stable liposomes was not enough to show a therapeutic effect (Cancer Chemother Pharmacol 49:201-210, 2002; Cancer Chemother Pharmacol 48:266-268, 2001, Eur J Cancer 37:2015-2022, 2001; Breast Cancer Res Treat 77:185-188, 2003; Lung Cancer 34:427-432, 2001; Cancer Chemother Pharmacol 50:131-136, 2002). It has been hypothesized that the enhanced release at the target site will significantly improve the specificity and efficacy of a liposomal drug (J Liposomes Res 8:299-335, 1998; Pharmaco Rev 51:691-744, 1999; Curt Opin Mol Ther 3:153-158, 2001). To solve this challenge, more research efforts were directed toward a triggered release, in response to a specific stimulus at a target site. Here, we present an engineered, bacterial channel protein as a remote-controlled nanovalve in sterically stable liposomes for a triggered release of the liposomal content on command.