Brain-targeted delivery of Tempol-loaded nanoparticles for neurological disorders.
Brain-targeted Tempol-loaded poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs) conjugated with a transferrin antibody (OX 26) were developed using the nanoprecipitation method. These NPs may have utility in treating neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Central to these diseases is an increased production of reactive oxygen and nitrogen species which may take part in the development of these conditions. As proof of principle, the NPs were loaded with Tempol, a free radical scavenger that has been shown to be protective against oxidative insults. To enhance the delivery of NPs to the central nervous system (CNS), we conjugated the transferrin receptor antibody covalently to PLGA NPs using the NHS-PEG3500-Maleimide crosslinker. The NPs showed a particle size suitable for blood brain barrier (BBB) permeation (particle size 80-110 nm) and demonstrated a sustained drug release behavior. A high cellular uptake of antibody-conjugated NPs was demonstrated in RG2 rat glioma cells. The ability of the Tempol-loaded NPs to prevent cell death by resveratrol in RG2 cells was determined using the MTT assay. The conjugated NPs containing Tempol were more effective in preventing cell viability by resveratrol when compared with unconjugated NPs or free Tempol in solution. Our findings suggest that transferrin-conjugated NPs containing antioxidants may be useful in the treatment of neurodegenerative diseases.
Department of Pharmaceutical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio 44272, USA.
Richard T
RT
Carroll
Deepak
D
Bhatia
Werner
W
Geldenhuys
Ruchi
R
Bhatia
Nicholas
N
Miladore
Anupam
A
Bishayee
Vijaykumar
V
Sutariya
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000378:metabolism*; D003692:Delayed-Action Preparations; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism*; D019344:Lactic Acid; D008301:Maleimides / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D013113:Spin Labels; D014168:Transferrin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D003432:Cross-Linking Reagents; D003497:Cyclic N-Oxides; D003692:Delayed-Action Preparations; D016166:Free Radical Scavengers; D008301:Maleimides; D013113:Spin Labels; D014168:Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C001803:tempol