The promoting effect of enteric materials on the oral absorption of larotaxel-loaded polymer-lipid hybrid nanoparticles

Enteric polymers have been found with absorption promotion effect on nanoparticles. To study the role of enteric polymers played in the process of oral nanoparticle delivery, Eudragit L100-55 (EU) and sodium alginate (SA) were selected as model enteric polymers and larotaxel (LTX) as model drug. Suspensions composed of LTX-loaded nanoparticles, HPMC and different enteric polymers (EU and SA) were prepared (NP@EU, NP@SA). And aspects like precipitate morphology upon contact with acid, nanoparticle encapsulation capability, in vitro drug release, intestinal residence and in vivo oral bioavailability were studied. It was found that precipitates formed by EU could encapsulate more NP in acidic environment than those of SA (>95% of EU vs. approximately 70% of SA), and this difference in NP encapsulation was found correlated with the morphology of the precipitates formed: precipitates of EU appeared as three dimensional granules with dense inner structure, while SA precipitated into film-like porous structures. Results of pharmacokinetic study indicated that both EU and SA were capable in improving LTX absorption with absolute bioavailability of 77.1% and 42.5%, respectively. And the better absorption promoting effect of NP@EU was correlated with its longer intestinal residence shown by the results of ex vivo imaging study. In conclusion, both EU and SA could improve the oral bioavailability of LTX-loaded NP, and NP encapsulation capability and intestinal residence time are considered as key factors affecting the degree of absorption promotion.



In conclusion, introduction of enteric polymers like Eudragit L100-55 or sodium alginate as an outer matrix is a feasible way promoting the oral bioavailability of LTX-loaded NP, with absolute bioavailability increased from 19.2% to 42.5% (SA) or 77.1% (EU), respectively. And the better performance of EU in promoting LTX oral absorption was attributed to its stronger NP encapsulation capability when forming precipitates in acidic environment, and the precipitates acted as a vehicle to reduce the movement rate of encapsulated NP, thus provided the nanoparticles with a widened time window for absorption. Based on this finding, future studies in exploring the oral absorption of functionalized nanoparticles in enteric polymers are warranted.


Continue on ScienceDirect