title: A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.
abstract: We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self-assembled nanocarrier for further oral chemotherapy. The teniposide loaded self-assembled nanocarrier (TSN) was spherical nanometric particles with narrow size distribution. The intestinal absorption of teniposide from TSN was obviously improved 4.09- and 6.35-fold in duodenum and jejunum at 0.5h after oral administration, then significantly decreased with the prolongation of time. The cellular uptake of TSN in Caco-2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time. Moreover, TSN could be internalized into Caco-2 cell monolayer through clathrin-mediated endocytosis pathway, and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway. The pharmacokinetic results indicated that the AUC(0-t) value of TSN in rats was significantly improved 5.41-fold than that of teniposide solution, moreover, the teniposide concentration in tumor from TSN was obviously improved over 7-fold in tumor bearing mice. The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model. Therefore, the self-assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Shijun
authors.initials: S
authors.lastname: Jiang
authors.forename: Zeying
authors.initials: Z
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Lingli
authors.initials: L
authors.lastname: Chen
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004386:Duodenum / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013713:Teniposide / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D013713:Teniposide