title: Multilayer micro-dispersing system as oral carriers for co-delivery of doxorubicin hydrochloride and P-gp inhibitor.
abstract: The primary constraints for efficient oral delivery of anticancer drugs include the efflux pump function of the multidrug transporter P-glycoprotein (P-gp) for anticancer drugs and the barriers to drug absorption in gastrointestinal (GI) tract. To improve bypassing P-gp drug efflux pumps and oral bioavailability of doxorubicin hydrochloride (DOX), Multilayer micro-dispersing system (MMS) was constructed by co-immobilization of DOX loaded chitosan/carboxymethyl chitosan nanogels (DOX:CS/CMCS-NGs), along with quercetin (Qu) in the core of multilayer sodium alginate beads (DOX:NGs/Qu-M-ALG-Beads). The obtained DOX:NGs/Qu-M-ALG-Beads possessed layer-by-layer structure and porous core with many nanoscale particles. The swelling characteristic and drug release results indicated that DOX:NGs/Qu-M-ALG-Beads exhibited favorable gastric acid tolerance and targeting release of intact DOX:CS/CMCS-NGs and Qu in small intestine. After oral administration of DOX:NGs/Qu-M-ALG-Beads in rats, DOX was effectively delivered into systemic circulation due to P-gp inhibitory properties of Qu. The absolute bioavailability reached 55.75%, about 18.65 folds higher than oral DOX. Tissue distribution results showed that the liver exhibited the highest DOX level, followed by kidney, heart, lung, and spleen. These results implied that DOX:NGs/Qu-M-ALG-Beads had great potential to be applied as dual drug delivery for oral chemotherapy.
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China. Electronic address: fengchao@ouc.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Feng
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Mu
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China; Department of Zoophysiology II, University of Kiel, Kiel, 24098, Germany.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
authors.forename: Mazhar Ali
authors.initials: MA
authors.lastname: Raja
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
authors.forename: Xiao Jie
authors.initials: XJ
authors.lastname: Cheng
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, China. Electronic address: xgchen@ouc.edu.cn.
authors.forename: Xi Guang
authors.initials: XG
authors.lastname: Chen
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D002214:Capsules; D002470:Cell Survival; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D010316:Particle Size; D011794:Quercetin / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000464:Alginates; D000903:Antibiotics, Antineoplastic; D002214:Capsules; D004337:Drug Carriers; D004317:Doxorubicin; D011794:Quercetin
keywords: Chitosan; Layer-by-layer; Oral anticancer-drug delivery