title: In vitro lipolysis and intestinal transport of β-arteether-loaded lipid-based drug delivery systems.
abstract: OBJECTIVE
  We aimed to assess the fate of β-arteether lipid-based drug delivery systems (AE-LBDDS) in terms of resistance to lipolysis and permeation across intestinal cells.
  
  
  METHODS
  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.
  
  
  RESULTS
  A higher level of AE precipitation was observed for formulations containing Cremophor EL (~30%) compared to formulations containing Tween 80 (~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 4°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.
  
  
  CONCLUSIONS
  LBDDS that are partly resistant to in vitro lipolysis significantly increased the transport of AE across intestinal cell monolayers.
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics & Drug Delivery Group, Université Catholique de Louvain, Avenue Mounier 73 B1.73.12, 1200, Brussels, Belgium.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Memvanga
authors.forename: Pierre
authors.initials: P
authors.lastname: Eloy
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gaigneaux
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D037621:Artemisinins / Q000737:chemistry*; D001692:Biological Transport; D018938:Caco-2 Cells; D018929:Cell Culture Techniques; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008066:Lipolysis; D008954:Models, Biological; D010539:Permeability; D010938:Plant Oils / Q000737:chemistry*; D012995:Solubility
chemical_list: D037621:Artemisinins; D004337:Drug Carriers; D010938:Plant Oils; C055141:artemotil