title: Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel.
abstract: BACKGROUND
  Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues.
  
  
  METHODS
  PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells.
  
  
  RESULTS
  Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, -11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, -5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg).
  
  
  CONCLUSIONS
  In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy.
authors.forename: Saeed
authors.initials: S
authors.lastname: Manoochehri
authors.forename: Behrad
authors.initials: B
authors.lastname: Darvishi
authors.forename: Golnaz
authors.initials: G
authors.lastname: Kamalinia
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Fallah
authors.forename: Seyed Naser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012709:Serum Albumin / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D012709:Serum Albumin; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid