title: Chitosan-based polyelectrolyte complexes as potential nanoparticulate carriers: physicochemical and biological characterization.
abstract: OBJECTIVE
  To investigate the effect of polyelectrolytes on the formation and physicochemical properties of chitosan nanoparticles (CS-NPs) used for the delivery of an anticancer drug, doxorubicin (DOX).
  
  
  METHODS
  Three DOX-loaded CS-NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS-DS/DOX NPs), and hyaluronic acid (CS-HA/DOX NPs) by using ionotropic gelation or complex coacervation.
  
  
  RESULTS
  CS-TP/DOX NPs were the smallest, with an average size of ~100 nm and a narrow size distribution, while CS-DS/DOX and CS-HA/DOX NPs were ~200 nm in size. Transmission electron microscopy clearly showed a spherical shape for all the NPs. The strong binding affinity of DOX for the multiple sulfate groups in DS resulted in a sustained release profile from CS-DS/DOX NPs at pH 7.4, while CS-HA/DOX NPs exhibited faster DOX release. This trend was also present under acidic conditions, where release of DOX was significantly augmented because of polymer protonation. Compared to CS-TP/DOX or CS-DS/DOX NPs, CS-HA/DOX NPs showed superior cellular uptake and cytotoxicity in MCF-7 and A-549 cells, because of their ability to undergo CD44-mediated endocytosis. Pharmacokinetic studies clearly showed that all CS-NPs tested significantly improved DOX plasma circulation time and decreased its elimination rate constant. Consistent with the in vitro release data, CS-DS/DOX NPs exhibited a relatively better DOX plasma profile and enhanced blood circulation, compared to CS-HA/DOX or CS-TP/DOX NPs. Overall, these results demonstrated how NP design can influence their function.
  
  
  CONCLUSIONS
  Taken together, CS-based polyelectrolyte complexes could provide a versatile delivery system with enormous potential in the pharmaceutical and biomedical sectors.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan, 712-749, South Korea.
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.forename: Tuan Hiep
authors.initials: TH
authors.lastname: Tran
authors.forename: Hyuk Jun
authors.initials: HJ
authors.lastname: Cho
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Jeon
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D004573:Electrolytes / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004573:Electrolytes; D004317:Doxorubicin; D048271:Chitosan