title: Modified-chitosan nanoparticles: Novel drug delivery systems improve oral bioavailability of doxorubicin.
abstract: The efficacy of most anticancer drugs is highly limited in vivo due mainly to poor pharmacokinetics behavior including poor bioavailability after extravascular administration. We have developed novel chitosan-modified polymeric nanoparticles for oral as well as i.v. administration. Nanoparticles were developed utilizing the double emulsion solvent evaporation technique for sustained delivery of various anticancer drugs. Chitosan diacetate (CDA) and chitosan triacetate (CTA) polymers were previously modified in our laboratory and used as novel matrix. Nanoparticles, loaded with various anticancer drugs, were characterized for particle size using dynamic light scattering as well as transmission electron microscopy and net surface charge using dynamic light scattering. Particles size was below 100nm in diameter and zeta potential ranged - (25-30). Encapsulation efficiency of anticancer drugs varied considerably and was dependent on the physicochemical characteristics of the encapsulated drug. However, chitosan triacetate nanoparticles showed relatively higher encapsulation efficiency than chitosan diacetate nanoparticles. In vitro release of encapsulated drugs was sustained over a period of 14days. Nanoparticles enhanced cellular accumulation of encapsulated drugs, compared to the free drugs, in vitro in MCF-7 and Caco-II tumor cell lines. In conclusion, diacetate and triacetate chitosan are novel polymers that can be used to formulate nanoparticles which efficiently encapsulated anticancer drugs, and sustained the release and enhanced tumor cellular uptake of these drugs. Further, chitosan triacetate nanoparticles enhanced oral bioavailability of doxorubicin. CDA and CTA nanoparticles can be used to efficiently deliver anticancer drugs and improve their in vivo profile.
authors.affiliation: Department of Pharmacy, American University of Madaba, Madaba, Jordan.
authors.forename: Ayman
authors.initials: A
authors.lastname: Khdair
authors.affiliation: Department of Pharmacy, American University of Madaba, Madaba, Jordan.
authors.forename: Islam
authors.initials: I
authors.lastname: Hamad
authors.affiliation: Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Hatim
authors.initials: H
authors.lastname: Alkhatib
authors.affiliation: Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Bustanji
authors.affiliation: Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mohammad
authors.affiliation: ACDIMA Biocenter, Amman, Jordan.
authors.forename: Rabab
authors.initials: R
authors.lastname: Tayem
authors.affiliation: Faculty of Pharmacy, The University of Jordan, Amman, Jordan. Electronic address: aiedeh@ju.edu.jo.
authors.forename: Khaled
authors.initials: K
authors.lastname: Aiedeh
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D004317:Doxorubicin; D048271:Chitosan
keywords: Anticancer; Cancer; Chitosan; Doxorubicin; Efflux; Emulsion; Imatinib; Nanoparticles; P-gp; Pemetrexed; Tumor; Vinblastine