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Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement |
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| Authors: | Zahra Karami Mohammad Reza Saghatchi Zanjani Saeed Rezaee Kobra Rostamizadeh |
| Affiliation: | 1. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran;2. Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran;3. Department of Clinical Sciences, Tabriz Branch, Islamic Azad University, Tabriz, Iran;4. Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran;5. Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran;6. Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran |
| Abstract: | Objective: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood–brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain. Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method. Results: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112?±?3.5?nm, 0.20?±?0.02, and ?33.2?±?2.6?mV, respectively. From in vivo studies in animal model of rats, the AUC0–4?h of brain concentration–time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug. Conclusions: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain. |
| Keywords: | Nanoemulsion lactoferrin indinavir blood–brain barrier neuropharmacokinetic |