title: Brain targeting with surface-modified poly(D,L-lactic-co-glycolic acid) nanoparticles delivered via carotid artery administration.
abstract: In this study, we investigated surface-modified nanoparticles (NP) formulated using a biodegradable polymer, poly(D,L-lactide-co-glycolide) (PLGA), for targeting central nervous system (CNS) diseases. Polysorbate 80 (P80), poloxamer 188 (P188), and chitosan (CS) were used to modify the surfaces of PLGA NP to improve the brain delivery of NP. Surface-modified PLGA NP were formulated using an emulsion solvent diffusion method. 6-Coumarin was used as a fluorescent label for NP. The different formulations of 6-coumarin-loaded PLGA NP were injected into rats via carotid arteries. NP remaining in the brain were evaluated quantitatively, and brain slices were observed using confocal laser scanning microscopy (CLSM). Carotid artery administration was more effective for delivering NP into the brain compared to intravenous administration. After administration, NP concentrations in the brain were increased by NP surface modification, especially CS- and P80-PLGA NP. CLSM observations indicated that P80-PLGA NP could cross the blood-brain barrier and thus serve as a drug delivery system for the CNS. These results indicate that surface-modified PLGA NP have a high potential for use in CNS delivery systems.
authors.affiliation: Laboratory of Pharmaceutical Engineering, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tahara
authors.forename: Yuta
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D001923:Brain Chemistry; D002339:Carotid Arteries; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid