Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability

Figures & data

Table 1 Solubility of baicalein in various vehicles

Oil	Solubility (mg/g)
Soybean oil	2.335±0.202
MCT	3.916±0.371
Capryol™ 90	4.476±0.283
Hemp oil	8.592±0.256
PM	24.88±0.524
Hemp oil/PM (10:1, w/w)	35.26±0.468

Notes: Solubility, milligram of baicalein in 1 g of vehicle; Capryol™ 90, propylene glycol monocaprylate. Data expressed as mean ± StD (n=3).

Abbreviations: MCT, medium-chain triglycerides; PM, poly(ethylene glycol) monooleate; StD, standard deviation.

Figure 1 Chemical structure of baicalein.

Figure 2 Effects of ratios of drug/excipients (A) and surfactants/oil (B) as well as homogenization cycle (C) with 20,000 psi on the particle size of BCL-NEs (mean ± StD, n=3), in which one factor was set as independent variable keeping other two factors as invariant. *P<0.05; **P<0.01.

Abbreviations: BCL, baicalein; NEs, nanoemulsions; StD, standard deviation.

Figure 3 Physical characterization of BCL-NEs: (A) size distribution, (B) appearance, and (C) TEM micrograph.

Abbreviations: BCL, baicalein; NEs, nanoemulsions; TEM, transmission electron microscopy.

Figure 4 Release profiles of BCL from nanoemulsions with the time in water, 0.1 M HCl, and PBS, pH 6.8 (n=3, mean ± StD).

Abbreviations: BCL, baicalein; PBS, phosphate-buffered saline; StD, standard deviation.

Table 2 Pharmacokinetic parameters of BCL in rats following oral administration of BCL suspensions, BCL emulsions, and BCL-NEs

Formulation	BCL suspensions	BCL emulsions	BCL-NEs
Cmax (μg/mL)	1.43±0.17	3.70±0.49	10.96±0.38*
Tmax (h)	4.23±0.26	2.14±0.33	1.96±0.25
AUC0–t (μg h/mL)	7.96±0.44	17.25±0.54	41.77±0.93*
T1/2 (h)	3.75±0.94	6.26±0.86	4.82±0.42
RBA (%)	–	216.7	524.7

Notes: AUC, area under the blood BCL concentration vs time curve; RBA compared with BCL suspensions. Data expressed as mean ± StD (n=6).

* P<0.01, significantly different from BCL emulsions and/or BCL suspensions. ‘–’ indicates not applicable.

Abbreviations: BCL, baicalein; RBA, relative bioavailability; NEs, nanoemulsions; StD, standard deviation.

Figure 5 Pharmacokinetic profiles of BCL in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs (n=6, mean ± StD).

Abbreviations: BCL, baicalein; NEs, nanoemulsions; StD, standard deviation.

Table 3 Effective intestinal permeability (P_eff) of free BCL and encapsulated BCL in NEs determined by the in situ single-pass intestinal perfusion

Intestinal segment	Peff
	Free BCL	BCL-NEs
Duodenum	1.512±0.225×10^−6	1.893±0.236×10^−5*
Jejunum	3.964±0.284×10^−6	2.652±0.334×10^−5*
Ileum	4.855±0.438×10^−6	6.078±0.124×10^−5*

Notes: Paired t-test. Data expressed as mean ± StD (n=8).

* P<0.01, significantly different from free BCL.

Abbreviations: BCL, baicalein; NEs, nanoemulsions; StD, standard deviation.

Figure 6 Cellular uptake of free BCL and BCL-NEs determined by the intracellular drug level (A) (mean ± StD, n=3) and cellular internalization of BCL-NEs evaluated by the CLSM imaging (B). *P<0.05; **P<0.01.

Abbreviations: BCL, baicalein; CLSM, confocal laser scanning microscopy; NEs, nanoemulsions; StD, standard deviation.

Figure 7 Relative cell viability of Caco-2 incubated with nanoemulsions with different BCL levels (n=3, mean ± StD).

Abbreviations: BCL, baicalein; StD, standard deviation.

Scheme 1 Illustrative diagram of the preparation of NEs and the oral delivery of BCL.

Abbreviations: BCL, baicalein; HPH, high-pressure homogenization; NEs, nanoemulsions; PM, poly(ethylene glycol) monooleate.