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Solid Lipid Nanoparticles Enhance the Delivery of the HIV Protease Inhibitor, Atazanavir, by a Human Brain Endothelial Cell Line

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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 ~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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Acknowledgments

This research is supported by a grant from the Ontario HIV Treatment Network awarded to Dr. R. Bendayan. The authors thank Mr. K. Babakhanian, Mr. B. Calvieri and Mr. S. Doyle for technical assistance with fluorescence and electron microscopy imaging.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada, M5S 3M2

    Niladri Chattopadhyay, Jason Zastre, Ho-Lun Wong, Xiao Yu Wu & Reina Bendayan

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  1. Niladri Chattopadhyay
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  2. Jason Zastre
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Correspondence to Reina Bendayan.

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Chattopadhyay, N., Zastre, J., Wong, HL. et al. Solid Lipid Nanoparticles Enhance the Delivery of the HIV Protease Inhibitor, Atazanavir, by a Human Brain Endothelial Cell Line. Pharm Res 25, 2262–2271 (2008). https://doi.org/10.1007/s11095-008-9615-2

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