Preparation, preliminary pharmacokinetics and brain tissue distribution of Tanshinone IIA and Tetramethylpyrazine composite nanoemulsions

Abstract

Objective: Tanshinone IIA (TSN) and Tetramethylpyrazine (TMP) were combined in a composite, oil-in-water nanoemulsions (TSN/TMP O/W NEs) was prepared to prolong in vitro and vivo circulation time, and enhance the bioavailability of TSN.

Material and methods: Physicochemical characterization of TSN/TMP O/W NEs was characterized systematically. The in vitro dissolution and in vivo pharmacokinetic experiments of TSN/TMP O/W NEs were also evaluated.

Result: A formulation was optimized, yielding a 32.5 nm average particle size, an encapsulation efficiency of over 95 %, and were spherical in shape as shown by TEM. TSN/TMP O/W NEs were shown to extend the release and availability in vitro compared to raw compounds. In pharmacokinetic study, the AUC_0→∞ and t_1/2 of the TSN/TMP O/W NEs were 481.50 mg/L*min and 346.39 min higher than TSN solution, respectively. Brain tissue concentration of TSN was enhanced with TSN/TMP O/W NEs over raw TSN and even TSN O/W NEs.

Conclusions: Therefore, nanoemulsions are an effective carrier to increase encapsulation efficiency of drugs, improve bioavailability and brain penetration for TSN – which is further enhanced by pairing with the co-delivery of TMP, providing a promising drug delivery.

KEYWORDS:

• Tanshinone IIA
• tetramethylpyrazine
• composite nanoemulsions
• bioavailability
• brain tissue distribution

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors acknowledge the funding support from the National Natural Science Foundation of China (51303006, 81703805), the Provincial Natural Science Foundation of Anhui Province (KJ2018ZD031, 1408085MH196), the University Excellent Top-notch Personnel Training fund of Anhui Province (gxfx2017050), and the Natural Science key Foundation of Anhui University of Chinese Medicine (2017zrzd013).