Brain targeting and toxicity study of odorranalectin-conjugated nanoparticles following intranasal administration

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Abstract
In order to improve brain uptake of nanoparticles following nasal administration, odorranalectin (OL), the smallest lectin with much less immunogenicity than other members of lectin family, was conjugated to the surface of poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP) in this study. The bioactivity of OLconjugated to the nanoparticles was verified by haemagglutination tests.Tissue distribution of OL-modified and unmodified nanoparticles (OL-NP and NP) wasevaluated following intranasal (i.n.) administration by in vivo fluorescence imaging technique using DiR as a tracer, comparing with that of unmodified nanoparticles after intravenous (i.v.) injection. Besides, the nasal toxicity of OL-NP was evaluated on Calu-3 cell lines, toad palate and rat nasal mucosa.The results of TEM examination and dynamic light scattering showed a generally spherical shape of OL-NP with an average volume-based diameter around 90 nm. The haemagglutination test proved thatOL retained its haemagglutination activity when conjugated to nanoparticles. The brain targeting indexes of NP andOL-NPfollowing i.n. administrationand NP following i.v. injection were 5.8, 11.6 and 0.08, respectively.Thus,i.n. administration demonstratedmuch better brain targetingefficiency thani.v. injection, and OL modificationfacilitatedthe nose-to-brain delivery of nanoparticles.Moreover, the toxicityassessment suggested good safety of OL-NPboth in vitro and in vivo.In summary, odorranalectin-conjugated nanoparticlecould be potentially used as a nose-to-brain drug deliverycarrierfor thetreatment of CNS diseases.

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