Drug delivery system for active brain targeting - Artificial Cells, Cell Engineering and Therapy - page 413

17.5 Survival of rats with an intracranially transplanted glioblastoma 101/8
after intravenous injection of doxorubicin (1.5mg/kg on days 2, 5 and 8) after
tumour transplantation using the following preparations: u (left line) untreated
controls, l empty nanoparticles coated with polysorbate 80, n doxorubicin in
saline, u (right line) doxorubicin-loaded nanoparticles, * doxorubicin in
polysorbate 80, s doxorubicin-loaded nanoparticles coated with polysorbate
80.
or apo B adsorb on the particle surface and then seem to promote the interaction
with the low-density lipoprotein (LDL) receptor followed by endocytotic uptake.
The nanoparticles thus would mimic the uptake of naturally occurring
lipoprotein particles. This hypothesis was supported by the achievement of an
anti-nociceptive effect using dalargin-loaded poly(butyl cyanoacrylate)
nanoparticles with adsorbed apo E or loperamide-loaded albumin nanoparticles
with covalently bound apo E.
Recently, a novel nanoparticle (NP) comprised of emulsifying wax and Brij 78
was shown to have significant brain uptake using the in situ rat brain perfusion
technique. To further these studies and to specifically target brain, Lockman et al.
(2003) have incorporated thiamine as a surface ligand on the nanoparticles. The
solid nanoparticles were prepared from oil-in-water microemulsion precursors.
Comparison of NP brain uptake demonstrated that the thiamine-coated
nanoparticles associated with the BBB thiamine transporter and had an increased
K in between 45 and 120 s. It was concluded that the thiamine ligand facilitated
binding and/or association with BBB thiamine transporters, which may be a
viable mechanism for nanoparticle mediated brain drug delivery.
Since cationic bovine serum albumin (CBSA) indicates a good accumulation
profile in the brain. Lu et al. (2005) studied a novel drug carrier for brain
delivery, CBSA conjugated with polyethyleneglycol±polylactide (PEG±PLA)
nanoparticle (CBSA-NP) (Fig. 17.6). Transmission electron micrograph (TEM)