title: OX26 modified hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) nanoparticles: synthesis, characterization and evaluation of its brain delivery ability.
abstract: A novel nanoparticles-based brain drug delivery system made of hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) which was surface functionalized with transferrin antibody (OX26) was prepared. Hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) was synthesized, characterized and applied to prepare nanoparticles by means of double emulsion solvent evaporation technique. Transmission electron micrograph and dynamic light scattering showed that nanoparticles had a round and regular shape with a mean diameter of 170 ± 20 nm. Surface chemical composition was detected by X-ray photoelectron spectroscopy. Endomorphins, as a model drug, was encapsulated in the nanoparticles. In vitro drug release study showed that endomorphins was released continuously for 72 h. Cellular uptake study showed that the uptake of nanoparticles by the brain microvascular endothelial cells was both time- and concentration-dependant. Further uptake inhibition study indicated that the uptake of nanoparticles was via a caveolae-mediated endocytic pathway. In vivo endomorphins brain delivery ability was evaluated based upon the rat model of chronic constriction injury of sciatic nerve. OX26 modified nanoparticles had achieved better analgesic effects, compared with other groups. Thus, OX26 modified hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) nanoparticles may be a promising brain drug delivery carrier.
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomaterial Research, Tianjin, People's Republic of China.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Bao
authors.forename: Xu
authors.initials: X
authors.lastname: Jin
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Lv
authors.forename: Tianjun
authors.initials: T
authors.lastname: Liu
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D005990:Glycerol / Q000737:chemistry*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000276:immunology
chemical_list: D000700:Analgesics; D000911:Antibodies, Monoclonal; D053769:Nanocapsules; D011108:Polymers; D014168:Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C043941:polyglycerol; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005990:Glycerol