文獻(xiàn)：Targeted delivery and triggered release of liposomal doxorubicin enhances cytotoxicity against human B lymphoma cells

作者：T Ishida a 1, M.J Kirchmeier a 2, E.H Moase a, S Zalipsky b, T.M Allen 

文獻(xiàn)鏈接：

https://www.sciencedirect.com/science/article/pii/S0005273601004096

摘要：

Since CFE is expected to contain cytoplasmic and lysosomal enzymes, the leakage of the hydrophilic, membrane-impermeable dye HPTS from formulations exposed to CFE may mimic the process of destabilization, in an intracellular environment, of liposomes stabilized with either mPEG-DSPE or mPEG-S-S-DSPE. CFE was adjusted to pH 5.5, approximating the lysosomal pH of between 5 and 6.5 [37], [38]. DOPE formulations, or DOPE formulations with 3 mol% mPEG-S-S-DSPE, released their contents in CFE with half-lives of 1.7 h (Fig. 3A). The release rate in CFE of the DOPE formulation with 5 mol% mPEG-S-S-DSPE was considerably slower; only 40% of encapsulated dye was released over 24 h (Fig. 3A). All three DOPE/CHEMS formulations, with or without mPEG-S-S-DSPE, released HPTS rapidly in CFE at pH 5.5; this release was almost complete by 8 h (Fig. 3B). DOPE/CHEMS and DOPE/CHEMS/mPEG-S-S-DSPE formulations incubated in CFE adjusted to pH 7.4 released HPTS at much slower rates (data not shown).

由于CFE預(yù)計(jì)含有細(xì)胞質(zhì)和溶酶體酶，親水性、膜不可滲透的染料HPTS從暴露于CFE的制劑中泄漏可能會(huì)模擬用mPEG-DSPE或mPEG-S-S-DSPE穩(wěn)定的脂質(zhì)體在細(xì)胞內(nèi)環(huán)境中的失穩(wěn)過(guò)程。

將CFE調(diào)節(jié)至pH 5.5，使溶酶體pH值接近5至6.5。DOPE制劑或含有3 mol%mPEG-S-S-DSPE的DOPE制劑在CFE中釋放其含量，半衰期為1.7小時(shí)。

含有5mol%mPEG-S-S-DSPE的DOPE制劑在CFE中的釋放速率明顯較慢；24小時(shí)內(nèi)僅釋放了40%的包封染料。所有三種DOPE/CHEMS制劑，無(wú)論是否含有mPEG-S-S-DSPE，在pH 5.5的CFE中都能快速釋放HPTS；8小時(shí)后，釋放幾乎完成。在pH 7.4的CFE中孵育的DOPE/CHEMS和DOPE/CHEMS/mPEG-S-S-DSPE制劑以慢得多的速率釋放HPTS。

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