title: Chitosan/o-carboxymethyl chitosan nanoparticles for efficient and safe oral anticancer drug delivery: in vitro and in vivo evaluation.
abstract: The present study investigated the ability of a polyelectrolyte complex (CS/CMCS-NPs), composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) as a pH responsive carrier for oral delivery of doxorubicin hydrochloride (DOX). The obtained CS/CMCS-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency and stability under the simulated GI tract conditions. The pH responsive stability of the DOX-loaded CS/CMCS nanoparticles (DOX:CS/CMCS-NPs) determined the drug release rate, which was lower in acidic pH than the neutral. Ex vivo intestinal adhesion and permeation indicated DOX:CS/CMCS-NGs were able to enhance absorption of DOX throughout the entire small intestine, especially in jejunum and ileum. Oral administration of DOX:CS/CMCS-NPs was effective to deliver DOX into blood, giving an absolute bioavailability of 42%. The tissue distribution and toxicity of DOX:CS/CMCS-NPs in rats showed low level of DOX in heart and kidney, and obviously decreased cardiac and renal toxicities. These results indicated CS/CMCS-NPs were highly efficient and safe as an oral delivery system for DOX.
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Feng
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wang
authors.forename: Changqing
authors.initials: C
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Cheng
authors.forename: Xiguang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001682:Biological Availability; D012634:Bodily Secretions / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007408:Intestinal Absorption; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C504164:O-carboxymethylchitosan; D008315:Malondialdehyde; D004317:Doxorubicin; D048271:Chitosan; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Carboxymethyl chitosan; Chitosan; Doxorubicin hydrochloride; Oral drug delivery; pH-responsive