title: Folate-decorated poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) nanoparticles for targeting delivery: optimization and in vivo antitumor activity.
abstract: BACKGROUND
  Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] nanoparticles [DOX/FA-PEG-P(HB-HO) NPs] have potential application in clinical treatments for cervical cancer due to specific affinity of folate and folate receptor in HeLa cells.
  
  
  OBJECTIVE
  The aim of this study was to develop an optimized formulation for DOX/FA-PEG-P(HB-HO) NPs, and investigate the targeting and efficacies of the nanoparticles.
  
  
  METHODS
  DOX/FA-PEG-P(HB-HO) NPs were prepared by W1/O/W2 solvent extraction/evaporation method, and an orthogonal experimental design [L9 (3(4))] was applied to establish the optimum conditions. The physico-chemical characteristics, microscopic observation and in vivo antitumor study of the nanoparticles were evaluated.
  
  
  RESULTS
  The optimum formulation was obtained with DOX 10% (w/v), FA-PEG-P(HB-HO) 6.5% (w/v), PVA 3%(w/v) and oil phase/internal water phase volume ratio of 3/1. The size distribution, drug loading and encapsulation efficiency of the optimized nanoparticles were 150-350 nm, 29.6 ± 2.9% and 83.5 ± 5.7%, respectively. In vitro release study demonstrated that 80% of the drug could release from the nanoparticles within 11 days. Furthermore, in vitro microscopic observation and in vivo antitumor study showed that DOX/FA-PEG-P(HB-HO) NPs could inhibit HeLa cells effectively, and the tumor inhibition rate (TIR) in vivo was 76.91%.
  
  
  CONCLUSIONS
  DOX/FA-PEG-P(HB-HO) NPs have been successfully developed and optimized. In vitro drug release study suggested a sustained release profile. Moreover, DOX/FA-PEG-P(HB-HO) NPs could effectively inhibit HeLa cells with satisfying targeting, and reduce side effects and toxicity to normal tissues. DOX/FA-PEG-P(HB-HO) NPs were superior in terms of inhibiting HeLa tumor over non-targeted formulations therapy.
authors.affiliation: a School of Environment and Safety, Taiyuan University of Science and Technology , Taiyuan , P.R. China .
authors.forename: Chan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: b College of Urban and Environmental Science, Liaoning Normal University , Dalian , P.R. China , and.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: c Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University , Taiyuan , P.R. China.
authors.forename: Liangqi
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation / Q000187:drug effects*; D005492:Folic Acid / Q000008:administration & dosage / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D000094122:Polyhydroxybutyrates
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D005492:Folic Acid; D011091:Polyesters; C476611:poly(3-hydroxybutyrate-co-3-hydroxyoctanoate); D000094122:Polyhydroxybutyrates
keywords: Doxorubicin; folate-targeted nanoparticles; in vivo antitumor activity; orthogonal design; poly(3-hydroxybutyrate-co-3-hydroxyoctanoate)