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

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Chattopadhyay N, Zastre J, Wong HL, Wu XY, Bendayan R

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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 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. This article was published in Pharm Res and referenced in Journal of Bioequivalence & Bioavailability

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