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.
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.
Authors: Paul R Lockman; Joanna Koziara; Karen E Roder; Jennifer Paulson; Thomas J Abbruscato; Russell J Mumper; David D Allen Journal: Pharm Res Date: 2003-05 Impact factor: 4.200
Authors: Rafael F Bressani; Ari S Nowacek; Sangya Singh; Shantanu Balkundi; Barrett Rabinow; Joellyn McMillan; Howard E Gendelman; Georgette D Kanmogne Journal: Nanotoxicology Date: 2010-12-22 Impact factor: 5.913
Authors: David J Mc Carthy; Meenakshi Malhotra; Aoife M O'Mahony; John F Cryan; Caitriona M O'Driscoll Journal: Pharm Res Date: 2014-12-02 Impact factor: 4.200