In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain
Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-{alpha} level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.
- OSTI ID:
- 21535240
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 251, Issue 1; Other Information: DOI: 10.1016/j.taap.2010.12.003; PII: S0041-008X(10)00452-7; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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ACETYLCHOLINE
AGGLUTININS
AMINO ACIDS
ENZYME IMMUNOASSAY
IN VIVO
LACTATE DEHYDROGENASE
LACTIC ACID
MICE
NANOSTRUCTURES
NOSE
OLFACTORY BULBS
PARTICLES
POLYETHYLENE GLYCOLS
RATS
TOXICITY
WHEAT
ALCOHOLS
AMMONIUM COMPOUNDS
ANIMALS
ANTIBODIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOASSAY
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CEREALS
DRUGS
ENZYMES
ESTERS
FACE
GLYCOLS
GRAMINEAE
HEAD
HEMIACETAL DEHYDROGENASES
HYDROXY ACIDS
HYDROXY COMPOUNDS
IMMUNOASSAY
LILIOPSIDA
MAGNOLIOPHYTA
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC POLYMERS
ORGANS
OXIDOREDUCTASES
PARASYMPATHOMIMETICS
PLANTS
POLYMERS
PROTEINS
QUATERNARY AMMONIUM COMPOUNDS
RESPIRATORY SYSTEM
RODENTS
VERTEBRATES