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.
Chattopadhyay
Niladri
N
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada, M5S 3M2.
Zastre
Jason
J
Wong
Ho-Lun
HL
Wu
Xiao Yu
XY
Bendayan
Reina
R
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