Aim

It was the aim of this study to synthesize a phosphorylated emulsifier possessing a PEG-linker for establishment of a potent zeta potential changing system in self-emulsifying drug delivery systems (SEDDS).

Methods

N,N'–Bis(polyoxyethylene)oleylamine (POA) was phosphorylated utilizing pyrophosphoric acid. Successful synthesis of POA bisphosphate (POAP) was confirmed by NMR and HR CS MAS. After incorporation of 1% POAP into SEDDS (Kolliphor RH 40, Capmul PG-8, Labrafac Lipophile WL 1349, Labrafac PG; 30/20/20/30, v/v), according emulsions were incubated with intestinal alkaline phosphatase (IAP) and the zeta potential was measured. Additionally, the amount of released phosphate upon incubation with IAP or on Caco-2 cells was quantified by malachite green assay. Finally, cell viability studies on Caco-2 cells were performed and mucus permeation properties with and without IAP preincubation were assessed.

Results

POAP was synthesized as brown viscous liquid with a yield of 36% and could be incorporated into SEDDS. By incubation with IAP a zeta potential shift from -15.1 to 6.5 mV was observed. A corresponding phosphate release in presence of isolated IAP as well as on Caco-2 cells was found. Assessment of the cytotoxic potential revealed no significant alteration in the safety profile of SEDDS by incorporation of POAP. Mucus permeation studies exposed a 2-fold higher permeation of fluorescein diacetate (FDA) having been embedded in SEDDS loaded with POAP in comparison to blank formulation and 3-fold higher permeability than for emulsions having been preincubated with phosphatase.

Conclusion

The novel phosphorylated surfactant exhibiting a PEG-linker facilitated a potent zeta potential change of SEDDS.

中文翻译：

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磷酸化PEG乳化剂：强大的工具，可开发zeta电位变化型自乳化药物递送系统（SEDDS）

目标

这项研究的目的是合成具有PEG接头的磷酸化乳化剂，以在自乳化药物递送系统（SEDDS）中建立有效的ζ电势改变系统。

方法

N，N'-双（聚氧乙烯）油胺（POA）被焦磷酸磷酸化。NMR和HR CS MAS证实了POA双磷酸酯（POAP）的成功合成。将1％POAP掺入SEDDS（Kolliphor RH 40，Capmul PG-8，Labrafac Lipophile WL 1349，Labrafac PG; 30/20/20/30，v / v）中后，将乳化液与肠碱性磷酸酶（IAP）一起孵育并测量了ζ电势。另外，通过孔雀石绿分析定量与IAP一起孵育或在Caco-2细胞上释放的磷酸盐的量。最后，对Caco-2细胞进行了细胞活力研究，并评估了有无IAP预温育的粘液渗透特性。

结果

POAP合成为棕色粘稠液体，产率为36％，可以掺入SEDDS中。通过与IAP孵育，观察到ζ电位从-15.1变为6.5 mV。发现在分离的IAP存在下以及在Caco-2细胞上相应的磷酸盐释放。对细胞毒性潜力的评估表明，通过掺入POAP，SEDDS的安全性没有明显改变。粘液渗透研究表明，与空白制剂相比，已嵌入装有POAP的SEDDS中的二乙酸荧光素（FDA）渗透率高2倍，而渗透率则比用磷酸酶预孵育的乳液高3倍。

结论

表现出PEG接头的新型磷酸化表面活性剂促进了SEDDS的有效Zeta电位变化。