title: Chitosan nanoparticles show rapid extrapulmonary tissue distribution and excretion with mild pulmonary inflammation to mice.
abstract: Pulmonary delivery of nanoparticles (NP) conjugated with therapeutic agents has been considered recently for both lung disorders and systemic circulation. Hydrophobically modified glycol chitosan (HGC) NP have previously shown excellent deposition to the tumor site and non-destructive intracellular release. Here, we evaluated the kinetics and toxicity of HGC NP by intratracheal instillation to mice. HGC NP showed a positive charge and average hydrodynamic size was around 350 nm. The half-life of NP in the lung was determined as 131.97±50.51 h. NP showed rapid uptake into systemic circulation and excretion via urine which was peaked at 6h after instillation. Although HGC NP were distributed to several extrapulmonary organs, the levels were extremely low and transient. HGC NP induced transient neutrophilic pulmonary inflammation from 6h to day 3 after instillation. Expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and chemokine (MIP-1α) in lung showed an increase from 1h to 24h after instillation and recovered thereafter. Our findings suggest that HGC NP can be successful candidates for use as pulmonary delivery vehicles, owing to their excellent biocompatibility, transiency, and low pulmonary toxicity, and property of rapid elimination without accumulation.
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Seoul, Republic of Korea.
authors.forename: Mina
authors.initials: M
authors.lastname: Choi
authors.forename: Minjung
authors.initials: M
authors.lastname: Cho
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Han
authors.forename: Jin
authors.initials: J
authors.lastname: Hong
authors.forename: Jayoung
authors.initials: J
authors.lastname: Jeong
authors.forename: Sangjin
authors.initials: S
authors.lastname: Park
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Wan-Seob
authors.initials: WS
authors.lastname: Cho
mesh_terms: D000818:Animals; D048271:Chitosan / Q000493:pharmacokinetics* / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced*; D014018:Tissue Distribution
chemical_list: D048271:Chitosan