title: Curcumin-loaded PLGA nanoparticles conjugated with anti- P-glycoprotein antibody to overcome multidrug resistance.
abstract: BACKGROUND
  The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur- NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrug- resistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo.
  
  
  METHODS
  First, we determined the MDR- reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions.
  
  
  RESULTS
  The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions.
  
  
  CONCLUSIONS
  Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand E-mail : pornngarm.d@cmu.ac.th.
authors.forename: Wanisa
authors.initials: W
authors.lastname: Punfa
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Supachai
authors.initials: S
authors.lastname: Yodkeeree
authors.forename: Taku
authors.initials: T
authors.lastname: Naiki
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Pornngarm
authors.initials: P
authors.lastname: Limtrakul
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage; D011100:Polyglycolic Acid / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin; D017239:Paclitaxel