Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement

被引：44

作者：

Karami, Zahra ^{[1
,2
]}

Zanjani, Mohammad Reza Saghatchi ^{[1
,2
,3
]}

Rezaeeb, Saeed ^{[2
,4
]}

Rostamizadeh, Kobra ^{[2
,5
]}

Hamidi, Mehrdad ^{[1
,2
]}

机构：

[1] Zanjan Univ Med Sci, Sch Pharm, Dept Pharmaceut Nanotechnol, Zanjan 4513956184, Iran

[2] Zanjan Univ Med Sci, Pharmaceut Nanotechnol Res Ctr, Zanjan, Iran

[3] Islamic Azad Univ, Dept Clin Sci, Tabriz Branch, Tabriz, Iran

[4] Zanjan Univ Med Sci, Sch Pharm, Dept Pharmaceut, Zanjan, Iran

[5] Zanjan Univ Med Sci, Sch Pharm, Dept Pharmaceut Biomat, Zanjan, Iran

来源：

DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY | 2019年 / 45卷 / 05期

关键词：

Nanoemulsion; lactoferrin; indinavir; blood-brain barrier; neuropharmacokinetic; CENTRAL-NERVOUS-SYSTEM; PARENTERAL NANOEMULSIONS; TARGETED DELIVERY; IN-VITRO; NANOPARTICLES; TRANSPORTERS; INFECTION; PROTEINS; DRUG;

D O I：

10.1080/03639045.2019.1569039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 AUC(0-4 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.

引用

页码：736 / 744

页数：9

共 39 条

[1] Nanoemulsion: for improved oral delivery of repaglinide [J].