Influences of molecular weight and particle size to intranasal drug delivery based on cell model of "nose-brain" / 中草药

ABSTRACT

Objective: To explore the factors affecting the nasal entry of the pharmaceutical preparations into the brain based on the established model of the "nose-brain" pathway in vitro. Methods: Calu-3 cells and OECs cells were co-cultured to construct a "nasal-brain" pathway cell model group. Taking fluorescein isothiocyanate dextran (FD) and fluorescent silver nanoparticles (AgNPs) as model drugs, the effects of drug molecular weight (Mw) factors and preparation particle size factors on the drug transnasal transport into the brain were explored. Results: The apparent permeability coefficient (Papp) of transcellular monolayer transport of FD decreased with the increase of molecular weight. The uptake of fluorescein isothiocyanate dextran with different molecular weights by OECs tended to be saturated after 90 min. As the molecular weight of FD increased, the uptake of OECs decreased significantly during the same uptake time. The apparent permeability coefficient of fluorescent AgNPs with different particle sizes in the "nose-brain" multi-channel cell model group of calu-3 monolayer decreased with the increase of the particle size of the nanoparticles. When the particle size was less than 40 nm, its transport characteristics in Calu-3 were shown as medium absorption (1 × 10-6 < Papp < 10 × 10-6), and when the particle size of nanoparticles was more than 60 nm, its transport characteristics were shown as difficult to absorb (Papp < 1 × 10-6). The uptake of OECs of fluorescent AgNPs with different particle sizes tended to be saturated at 60 min, and with the increase of the particle size of fluorescent AgNPs, the uptake of OECs at the same uptake time showed a significant decline. Conclusions The Mw of the drug and the particle size of the nano-formulation have an important influence on the nasal transport of the drug into the brain. Drugs with a molecular weight of < 4 000 and nano particles with a particle size of less than 40 nm have better transport and uptake characteristics.