Solid lipid nanoparticles enhance the delivery of the HIV protease inhibitor, atazanavir, by a human brain endothelial cell line.
OBJECTIVE
Protease inhibitors (PIs) exhibit low brain permeability. As a result, unchallenged HIV viral replication can lead to HIV-encephalitis and antiretroviral drug resistance. The objective of this study was to develop and evaluate a lipid nanoparticle system for enhanced brain delivery of the potent and frequently used HIV PI, atazanavir, using a well characterized human brain microvessel endothelial cell line (hCMEC/D3) representative of the blood-brain barrier.


METHODS
Solid lipid nanoparticles (SLNs) were prepared by a thin film hydration technique and analyzed for atazanavir encapsulation efficiency, particle size, morphology, zeta potential and drug release. Cell viability experiments demonstrate that SLNs exhibit no toxicity in hCMEC/D3 cells up to a concentration corresponding to 200 nM of atazanavir.


RESULTS
Spherical SLNs with an average particle size of approximately 167 nm were formulated. Delivery of [3H]-atazanavir by SLNs led to a significantly higher accumulation by the endothelial cell monolayer as compared to the drug aqueous solution. Furthermore, release of Rhodamine-123 (a fluorescent probe) by SLNs also resulted in a higher cellular accumulation.


CONCLUSIONS
These data suggest that SLNs could be a promising drug delivery system to enhance brain uptake of atazanavir and potentially other PIs.
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada, M5S 3M2.
Niladri
N
Chattopadhyay
Jason
J
Zastre
Ho-Lun
HL
Wong
Xiao Yu
XY
Wu
Reina
R
Bendayan
D000069446:Atazanavir Sulfate; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D042783:Endothelial Cells / Q000378:metabolism*; D005456:Fluorescent Dyes; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010316:Particle Size; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D020112:Rhodamine 123; D012995:Solubility
D004337:Drug Carriers; D005456:Fluorescent Dyes; D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D020112:Rhodamine 123; D000069446:Atazanavir Sulfate