Solid lipid nanoparticles enhance the delivery of the HIV protease inhibitor, atazanavir, by a human brain endothelial cell line

  • Pharm Res. 2008 Oct;25(10):2262-71. doi: 10.1007/s11095-008-9615-2.
Niladri Chattopadhyay  1 ,  Jason Zastre ,  Ho-Lun Wong ,  Xiao Yu Wu ,  Reina Bendayan
Affiliations
  • 1. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada, M5S 3M2.
PMID: 18516666 DOI: 10.1007/s11095-008-9615-2
Abstract

Purpose: 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.

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