文獻：Synthesis and Evaluation of a Novel Lipophilic Folate Receptor Targeting Ligand

作者：YING LIU, SONGLIN XU, LESHENG TENG, BRYANT YUNG, JING ZHU, HONG DING and ROBERT J. LEE

文獻鏈接：https://ar.iiarjournals.org/content/31/5/1521.short

摘要：

Background: Folate receptor (FR)-targeted liposomes have been investigated as delivery vehicles for anticancer drugs. A novel lipophilic FR ligand, folate-glutathione-polyethyleneglycol-distearoyl phosphatidylethanolamine (F-GSH-PEG-DSPE), was synthesized, incorporated into liposomes and evaluated for FR targeting efficiency. These liposomes were then evaluated as carriers of the chemotherapy agent vincristine (VIN). Materials and Methods: F-GSH-PEG-DSPE was synthesized and FR-targeted liposomes loaded with either calcein (F-L-Calcein) or VIN (F-L-VIN) were prepared by thin film hydration followed by polycarbonate membrane extrusion and, in the case of VIN, by remote loading. To assess liposome stability, the uptake of F-L-VIN in KB (FR+) cancer cells was measured after storage under 4°C for 3 months. Comparative pharmacokinetic studies were carried out with F-L-VIN and L-VIN (non-targeted control liposomes). Results: F-L-Calcein showed significantly higher cellular uptake in KB cells compared to non-targeted liposomes. In addition, F-L-VIN showed enhanced cytotoxicity in KB cells in vitro compared to control liposomes. Pharmacokinetic parameters indicated that both F-L-VIN and control liposomes had higher area under the curve (AUC), mean residence time (MRT), elimination half life (t1/2-β) and lower total body clearance (CL) than those of free VIN, while there were no significant differences between these liposomal formulations. Conclusion: F-GSH-PEG-DSPE is effective as a novel ligand for the synthesis of FR-targeted liposomes.

合成了一種新型親脂性FR配體，葉酸-谷胱甘肽聚乙二醇二硬脂酰磷脂酰乙醇胺（F-GSH-PEG-DSPE），將其摻入脂質體中，并評估了FR靶向效率。然后將這些脂質體作為化療藥物長春新堿（VIN）的載體進行評估。

材料和方法：合成F-GSH-PEG-DSPE，通過薄膜水合、聚碳酸酯膜擠出和遠程加載制備負載鈣黃綠素（F-L-calcein）或VIN（F-L-VIN）的FR靶向脂質體。

為了評估脂質體的穩定性，在4°C下儲存3個月后，測量KB（FR+）細胞對F-L-VIN的攝取。用F-L-VIN和L-VIN（非靶向對照脂質體）進行了比較藥代動力學研究。

結果：與非靶向脂質體相比，F-L-Calcein在KB細胞中的細胞攝取明顯更高。此外，與對照脂質體相比，F-L-VIN在體外KB細胞中顯示出增強的細胞毒性。

藥代動力學參數表明，F-L-VIN和對照脂質體的曲線下面積（AUC）、平均停留時間（MRT）、消除半衰期（t1/2-β）和全身清除率（CL）均高于游離VIN，但這些脂質體制劑之間沒有顯著差異。

結論：F-GSH-PEG-DSPE作為合成FR靶向脂質體的新型配體是有效的。

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