概況

納米晶自穩定Pickering乳液（NSSPE）是一種僅以難溶性成分自身納米晶為穩定劑的新型乳液。以川芎油為主要油相的NSSPE可顯著促進葛根素（Pu）的口服吸收。該研究旨對其口服促吸收機制進行探討。通過體外溶出試驗揭示NSSPE對Pu溶出的影響;通過Caco-2細胞攝取和雙向轉運試驗,探討NSSPE對Pu腸道細胞吸收和轉運的影響及機制。結果顯示,NSSPE的釋藥速率與納米晶相似,累積溶出率都顯著高於原料藥,且不受釋藥介質pH的影響。NSSPE中Pu的攝取具有濃度依賴性,且顯著高於溶液和表面活性劑乳。與脂筏/小窩蛋白介導有關的抑制劑染料木素、吲哚美辛能顯著降低NSSPE中Pu的攝取率。與溶液相比,NSSPE和表面活性劑乳液均顯著提高了Pu AP→BL方向的轉運速率K_a和表觀滲透係數P_app,但BL→AP方向的轉運無顯著性差異。可見,該NSSPE中Pu的Caco-2細胞吸收同時存在被動轉運和主動轉運,以及脂筏/小窩蛋白介導的胞飲;其促進Pu口服吸收的機制與NSSPE中Pu以納米晶形式存在,可促進溶出,以及用作油相的川芎油可促進藥物跨膜轉運、抑制外排有關。正是NSSPE的這種獨特結構和組成促進了Pu的口服吸收。

Nanocrystals self-stabilized Pickering emulsion (NSSPE) is a new kind of emulsion where only nanocrystals of poorly soluble drugs are used as stabilizers. Our previous study showed that NSSPE with Ligusticum chuanxiong oil as the main oil phase can significantly promote oral absorption of puerarin. The present  study  aimed to explore its absorption mechanism in oral administration. The in vitro dissolution test was carried out to study the effect of NSSPE on release of puerarin. The effects and mechanism of NSSPE on uptake and transport of puerarin across Caco-2 cell were investigated. The results showed that the drug release rate of NSSPE was similar to that of nanocrystals, with their cumulative dissolution of puerarin not affected by pH of releasing mediums, both significantly higher than that of crude material. The uptake of puerarin in NSSPE was concentration-dependent and significantly higher than that of solution or surfactant stabilized emulsion. Genistein and indomethacin, inhibitors of lipid rafts / caveolin, could significantly reduce the uptake of puerarin in NSSPE. Compared with solution, NSSPE and surfactants stabilized emulsion obviously increased transport rate K_a and apparent permeability coefficient P_app of puerarin in AP → BL direction, but there was no significant difference in BL → AP direction. It could be inferred that there were both passive and active transport mechanisms, as well as lipid raft / caveolin mediated endocytosis for absorption of NSSPE. The promoted oral absorption of puerarin in NSSPE was mainly related to the existing nanocrystal form which could promote dissolution, puerarin as well as Ligusticum chuanxiong oil which could promote drug transmembrane transport and inhibit drug efflux. It is the unique structure and composition of the compound NSSPE that promoted the oral absorption of puerarin.