title: Preparation and evaluation of Baicalin-loaded cationic solid lipid nanoparticles conjugated with OX26 for improved delivery across the BBB.
abstract: OBJECTIVE
  A novel brain targeting drug delivery system based on OX26 antibody conjugation on PEGylated cationic solid lipid nanoparticles (OX26-PEG-CSLN) was prepared.
  
  
  METHODS
  The Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) were prepared by emulsion evaporation-solidification at low temperature method. The immune-gold labeled OX26-PEG-CSLN was visualized by transmission electron microscopy. The mean diameter and zeta potential of OX26-PEG-CSLN, PEG-CSLN and CSLN were determined using a Zetasizer. The entrapment efficiency of OX26-PEG-CSLN, PEG-CSLN and CSLN was determined by ultrafiltration centrifugation method. And the solid-state characterization of OX26-PEG-CSLN and CSLN were analyzed by X-ray. Pharmacokinetics studies were conducted by in vivo microdialysis in rat cerebrospinal fluid.
  
  
  RESULTS
  The results showed that the OX26-PEG-CSLN, PEG-CSLN and CSLN had average diameters of 47.68 ± 1.65, 27.20 ± 1.70 and 33.89 ± 5.74 nm, Zeta potentials of -0.533 ± 0.115 mV, 11.200 ± 0.500 mV and 11.080 ± 1.170 mV and entrapment efficiencies of 83.03 ± 0.01%, 92.90 ± 3.50% and 97.83 ± 0.19%, respectively. In the pharmacokinetics studies, the AUC value of OX26-PEG-CSLN was11.08-fold higher than that of the Baicalin solution (SOL) (p<0.01), and 1.12-fold higher than that of the CSLN (p>0.05); the Cmax value of OX26-PEG-CSLN was 7.88-fold higher than that of SOL (p<0.01) and 1.12-fold (p<0.01) higher than that of the CSLN, respectively.
  
  
  CONCLUSIONS
  These results demonstrated OX26-PEG-CSLN could be a promising carrier to deliver drugs across the BBB for the treatment of brain diseases.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin , P.R. China .
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.forename: Hainan
authors.initials: H
authors.lastname: Zhao
authors.forename: Lexin
authors.initials: L
authors.lastname: Shu
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: ChukwunweikeIkechukwu
authors.initials: C
authors.lastname: Okeke
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002412:Cations; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005419:Flavonoids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D008055:Lipids; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014961:X-Ray Diffraction
chemical_list: D000911:Antibodies, Monoclonal; D002412:Cations; D004337:Drug Carriers; D005419:Flavonoids; D008055:Lipids; C038044:baicalin; D011092:Polyethylene Glycols
keywords: BBB; Baicalin; OX26; brain target drug delivery; cationic solid lipid nanoparticles