Application of Virus Targeting Nanocarrier Drug Delivery System in Virus-Induced Central Nervous System Disease Treatment

Abstract

Virus-induced central nervous system (CNS) diseases represent a significant burden to animal health worldwide. The difficulty in treating these diseases is mainly attributable to the elaborate barrier system, which limits the transport of drugs to the infected sites. Therefore, it is necessary to develop smart delivery technologies for treatment of these diseases. In the study, viral nervous necrosis disease was studied as a model to evaluate the feasibility of multiwalled carbon nanotubes (MWCNTs) conjugated with virus-specific nanobody and antiviral drug for targeted therapy of virus-induced CNS diseases. The virus (named as PGNNV) was isolated, identified and purified from diseased grouper. A nai ̈ve phage-displayed alpaca nanobody library was constructed, and the purified PGNNV was used for biopanning of PGNNVspecific nanobody from the library. The targeted delivery system based on MWCNTs conjugated with polyethylenimine, ribavirin, and PGNNV-specific nanobody was constructed and designated as MWCNTs-PEI-R-Nb. Targeting ability and treatment effects of the MWCNTs-PEI-R-Nb were checked both in vitro and in vivo. MWCNTs-PEI-R-Nb showed an increasing distribution in PGNNV-infected cells, and an obvious accumulation in the brain of PGNNV-infected zebrafish larvae. MWCNTs-PEI-R-Nb also showed a strong anti-PGNNV ability both in vitro and in vivo. The mortality of larvae treated with MWCNTs-PEI-R-Nb (equivalent to 100 mg/L ribavirin) was 27% during 10 days post infection, whereas it was 100% for the control group. The results so far indicate that MWCNTs conjugated with antiviral drugs and viral-specific antibody are effective means for virus-induced CNS disease targeted therapy.

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers

“…These mechanisms are also known as independent energy and dependent energy pathways, respectively. 42,43 Table 2 describes the current literature summarizing CNT entry into various cells, with a focus on dimension, cell type and CNT surface functionalization.…”

Betanodavirus and VER Disease: A 30-year Research Review

“…In this assay, zebra fish infected with pearl grouper nervous necrosis virus (PGNNV) was exposed to MWCNTs conjugated with polyethylenimine, ribavirin and PGNNV-specific nanobody. Results obtained indicated an obvious accumulation of the nanotubes in the brain of infected fish and a strong anti-PGNNV activity [322].…”

Advances in Drug Delivery Nanosystems Using Graphene-Based Materials and Carbon Nanotubes

“…Cidofovir (Figure 4)-loaded MWCNTs modified with cyclodextrins and branched PEI and doped with Rhodamine crossed the cell membrane via the clathrin-dependent pathway and co-localized in the lysosomal compartment; the powerful escape of drug from lysosome and its release close to the nuclear region induced the antiviral activity [284]. MWCNTs conjugated with PEI, an antiviral drug ribavirin (Figure 4) and the pearl gentian grouper nervous necrosis virus (PGNNV)-specific nanobody showed an increasing distribution in PGNNV-infected cells, powerful anti-PGNNV ability both in vitro and in vivo and such formulations can be an effective tool for virus-induced central nervous system disease targeted therapy [285]. PCL/poly(N-vinyl-2-pyrrolidone) (PVP) core-shell nanofibers showing mean diameter 300-400 nm and containing MWCNTs and 5-FU loaded in the core of these nanofibers showed sustained and prolonged drug release (up to 85% after 528 h) and cytotoxicity against HeLa cells (50.35% after 72 h), suggesting that this drug delivery system can be applied in post-surgical delivery of anticancer drugs [286].…”