In Vitro Lipolysis and Intestinal Transport of β-Arteether-Loaded Lipid-Based Drug Delivery Systems

We aimed to assess the fate of beta-arteether lipid-based drug delivery systems (AE-LBDDS) in terms of resistance to lipolysis and permeation across intestinal cells. AE-LBDDS contained Tween 80 or Cremophor EL as surfactants, ethanol, Maisine 35-1 and vegetable oil. The solubilization behavior of AE was investigated during dynamic in vitro lipolysis. The permeation of AE-LBDDS was evaluated using Caco-2, HT29-MTX and M cell monolayers. A higher level of AE precipitation was observed for formulations containing Cremophor EL (similar to 30%) compared to formulations containing Tween 80 (similar to 10%) after lipolysis. However, rapid re-dissolution of the precipitated AE from LBDDS containing Cremophor EL in the intestinal biorelevant media was observed. The transport of AE loaded in LBDDS was enhanced in comparison to that of free drug due to the increased AE solubility. The apparent permeability of all AE-LBDDS across Caco-2 cell monolayers was approximately 3.10(-6) cm/s. A decrease in the permeability was observed at 4A degrees C. M cells did not influence the transport of AE-LBDDS, and mucus decreased AE permeability when formulated with Tween 80. Furthermore, AE is not a P-glycoprotein substrate. LBDDS that are partly resistant to in vitro lipolysis significantly increased the transport of AE across intestinal cell monolayers.