β-cyclodextrin-poly(β-amino ester) nanoparticles for sustained drug delivery across the blood-brain barrier.
Novel biodegradable polymeric nanoparticles composed of β-cyclodextrin and poly(β-amino ester) segments have been developed for sustained drug delivery across the blood-brain barrier (BBB). The nanoparticles have been synthesized by cross-linking β-cyclodextrin with poly(β-amino ester) via the Michael addition method. The chemical, physical, and degradation properties of the nanoparticles have been characterized by matrix-assisted laser desoption/ionization time-of-flight, attenuated total reflectance Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and atomic force microscopy techniques. Bovine and human brain microvascular endothelial cell monolayers have been constructed as in vitro BBB models. Preliminary results show that the nanoparticles do not affect the integrity of the in vitro BBB models, and the nanoparticles have much higher permeability than dextran control across the in vitro BBB models. Doxorubicin has been loaded into the nanoparticles with a loading efficiency of 86%, and can be released from the nanoparticles for at least one month. The developed β-cyclodextrin-poly(β-amino ester) nanoparticles might be useful as drug carriers for transporting drugs across the BBB to treat chronic diseases in the brain.
Department of Surgery, Pennsylvania State University, Hershey, PA 17033, USA.
Eun Seok
ES
Gil
Linfeng
L
Wu
Lichong
L
Xu
Tao Lu
TL
Lowe
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D002417:Cattle; D002478:Cells, Cultured; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D042783:Endothelial Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D055806:Microvessels; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000378:metabolism*
D004337:Drug Carriers; D011108:Polymers; D047392:beta-Cyclodextrins; C507253:poly(beta-amino ester); D004317:Doxorubicin