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. 2019 Sep 6:14:7291-7306.
doi: 10.2147/IJN.S214883. eCollection 2019.

Oral absorption and lymphatic transport of baicalein following drug-phospholipid complex incorporation in self-microemulsifying drug delivery systems

Hengfeng Liao  1   2 , Yue Gao  1   2 , Chunfang Lian  1   2 , Yun Zhang  1   2 , Bangyuan Wang  1   2 , Yanfang Yang  1   2 , Jun Ye  1   2 , Yu Feng  1   2 , Yuling Liu  1   2
Affiliations

Oral absorption and lymphatic transport of baicalein following drug-phospholipid complex incorporation in self-microemulsifying drug delivery systems

Hengfeng Liao et al. Int J Nanomedicine. .

Abstract

Purpose: The aims of this study were to prepare a baicalein self-microemulsion with baicalein-phospholipid complex as the intermediate (BAPC-SMEDDS) and to compare its effects with those of conventional baicalein self-microemulsion (CBA-SMEDDS) on baicalein oral absorption and lymphatic transport.

Methods: Two SMEDDS were characterized by emulsifying efficiency, droplet size, zeta potential, cloud point, dilution stability, physical stability, and in vitro release and lipolysis. Different formulations of 40 mg/kg baicalein were orally administered to Sprague-Dawley rats to investigate their respective bioavailabilities. The chylomicron flow blocking rat model was used to evaluate their lymphatic transport.

Results: The droplet sizes of BAPC-SMEDDS and CBA-SMEDDS after 100x dilution were 9.6±0.2 nm and 11.3±0.4 nm, respectively. In vivo experiments indicated that the relative bioavailability of CBA-SMEDDS and BAPC-SMEDDS was 342.5% and 448.7% compared to that of free baicalein (BA). The AUC0-t and Cmax of BAPC-SMEDDS were 1.31 and 1.87 times higher than those of CBA-SMEDDS, respectively. The lymphatic transport study revealed that 81.2% of orally absorbed BA entered the circulation directly through the portal vein, whereas approximately 18.8% was transported into the blood via lymphatic transport. CBA-SMEDDS and BAPC-SMEDDS increased the lymphatic transport ratio of BA from 18.8% to 56.2% and 70.2%, respectively. Therefore, self-microemulsion not only significantly improves oral bioavailability of baicalein, but also increases the proportion lymphatically transported. This is beneficial to the direct interaction of baicalein with relevant immune cells in the lymphatic system and for proper display of its effects.

Conclusion: This study demonstrates the oral absorption and lymphatic transport characteristics of free baicalein and baicalein SMEDDS with different compositions. This is of great significance to studies on lymphatic targeted delivery of natural immunomodulatory compounds.

Keywords: SMEDDS; baicalein; lymphatic transport; oral bioavailability; phospholipid complex.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The TEM pictures of BAPC-SMEDDS and CBA-SMEDDS. Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions.
Figure 2
Figure 2
The size distribution of BAPC-SMEDDS and CBA-SMEDDS, which were subjected to different folds of dilution with purified water (n=3). Notes: A, dilution ratio (1:5–1:1000); B, dilution ratio (1:5–1:100). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions.
Figure 3
Figure 3
Delta transmission (△t) and turbiscan stability index (TSI) profiles of BAPC-SMEDDS and CBA-SMEDDS by using Turbiscan TOWER. Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions.
Figure 4
Figure 4
Release profile of baicalein from BAPC-SMEDDS, CBA-SMEDDS and BA (pH1.0, n=3). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions; BA, free baicalein.
Figure 5
Figure 5
Release profile of baicalein from BAPC-SMEDDS, CBA-SMEDDS and BA (pH6.8, n=3). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions; BA, free baicalein.
Figure 6
Figure 6
Consumption of 0.1 M NaOH during lipolysis of blank-SMEDDS with or without phospholipid (n=3). Abbreviations: K-PC-SMEDDS, blank SMEDDS with phospholipid; K-SMEDDS, blank SMEDDS without phospholipid.
Figure 7
Figure 7
Mean droplet size of microemulsion globules or micelles formed during the in vitro lipolysis (n=3). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions.
Figure 8
Figure 8
Distribution of baicalein in aqueous phase during lipolysis of BAPC-SMEDDS and CBA-SMEDDS (n=3). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions.
Figure 9
Figure 9
Mean plasma concentration–time curves of baicalin in rats after oral administration of BAPC-SMEDDS, CBA-SMEDDS and BA (n=5). Notes: The data were presented as mean ± SD (n=5). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions; BA, free baicalein.
Figure 10
Figure 10
Mean plasma concentration–time curves of baicalein in rats after oral administration of BAPC-SMEDDS, CBA-SMEDDS and BA (n=5). Notes: The data were presented as mean ± SD (n=5). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions; BA, free baicalein.
Figure 11
Figure 11
The average AUC0-t and Cmax of baicalein after oral administration of BAPC-SMEDDS, CBA-SMEDDS and BA (n=5). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions; BA, free baicalein; AUC, area under the curve; Cmax, peak concentration.
Figure 12
Figure 12
Mean plasma concentration–time curves of baicalin in rats within 3 hrs after intraperitoneal pretreatment with or without 3.0 mg/kg cycloheximide following oral administration of BAPC-SMEDDS, CBA-SMEDDS and BA (n=5). Notes: A, intraperitoneal pretreatment with or without 3.0 mg/kg cycloheximide following oral administration of BAPC-SMEDDS; B, intraperitoneal pretreatment with or without 3.0 mg/kg cycloheximide following oral administration of CBA-SMEDDS; C, intraperitoneal pretreatment with or without 3.0 mg/kg cycloheximide following oral administration of BA. The data were presented as mean ± SD (n=5). Abbreviations: BAPC-SMEDDS, baicalein-phospholipid complex self-microemulsions; CBA-SMEDDS, conventional baicalein self-microemulsions; BA, free baicalein.
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