Xingnaojing mPEG₂₀₀₀-PLA modified microemulsion for transnasal delivery: pharmacokinetic and brain-targeting evaluation

Abstract

Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. In order to decrease the XNJ-M-induced mucosal irritation, XNJ-M modified by mPEG₂₀₀₀-PLA (XNJ-MM) were prepared in a previous work. The present work aimed to assess the impact of mPEG₂₀₀₀-PLA on pharmacokinetic features and brain-targeting ability of XNJ-M. The bioavailability and brain-target effects of borneol and geniposide in XNJ-M and XNJ-MM were compared in mice after intravenous (i.v.) and intranasal (i.n.) administrations. Gas chromatography, high-performance liquid chromatography, and ultra-performance liquid chromatography/tandem mass spectrometry methods were developed for the quantification of borneol and geniposide. Blood and brain samples were collected from mice at different time points after i.v. and i.n. treatments with borneol at 8.0 mg/kg, geniposide at 4.12 mg/kg. In addition, near-infrared fluorescence dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine iodide was loaded into microemulsions to evaluate the brain-targeting ability of XNJ-M and XNJ-MM by near-infrared fluorescence imaging in vivo and ex vivo. For XNJ-M and XNJ-MM, the relative brain targeted coefficients (Re) were 134.59% and 198.09% (borneol), 89.70% and 188.33% (geniposide), respectively. Besides, significant near-infrared fluorescent signal was detected in the brain after i.n. administration of microemulsions, compared with that of groups for i.v. administration. These findings indicated that mPEG₂₀₀₀-PLA modified microemulsion improved drug entry into blood and brain compared with normal microemulsion: the introduction of mPEG₂₀₀₀-PLA in microemulsion resulted in brain-targeting enhancement of both fat-soluble and water-soluble drugs. These findings provide a basis for the significance of mPEG₂₀₀₀-PLA addition in microemulsion, defining its effects on the drugs in microemulsion.

• Borneol
• geniposide
• microemulsion
• mPEG₂₀₀₀-PLA
• pharmacokinetics
• Xingnaojing

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of this article. This work was supported by the National Natural Science Foundation of China (No. 81102816) and Independent Research Project of Beijing University of Chinese Medicine (No. 2013-JYBZZ-XS-083).