Biotinylated-lipid bilayer coated mesoporous silica nanoparticles for improving the bioavailability and anti-leukaemia activity of Tanshinone IIA

Figures & data

Figure 1. Chemical structure of TanIIA.

Figure 2. Size distribution (a) and TEM images (b) of TanIIA@MSNs (A), TanIIA@LB-MSNs (B) and TanIIA@Bio-LB-MSNs (C). Scale bars for TEM images are 100 nm, 50 and 50 for A, B and C, respectively.

Figure 3. FTIR spectra of the Bio-liposomes, TanIIA@MSNs and TanIIA@Bio-LB-MSNs.

Figure 4. The nitrogen adsorption–desorption isotherms of the MSNs and TanIIA@MSNs.

Table 1. Characterization concerning the size, polydispersity and zeta potential of TanIIA@MSNs, TanIIA@LB-MSNs and TanIIA@Bio-LB-MSNs.

Sample	Particle size (nm)	PDI	Zeta potential (mV)
TanIIA@MSNs	282.4 ± 8.8	0.232 ± 0.022	−28.9 ± 0.8
TanIIA@LB-MSNs	288.0 ± 4.6	0.135 ± 0.041	−51.2 ± 1.5
TanIIA@Bio-LB-MSNs	288.8 ± 2.0	0.158 ± 0.021	−45.6 ± 0.6

Table 2. The nitrogen adsorption–desorption characteristic parameters of MSNs and TanIIA@MSNs.

Sample	BET surface area (m^2/g)	Pore volume (m^3/g)	Pore size (nm)
MSNs	1139.8	1.2	4.2
TanIIA@MSNs	269.5	0.6	1.7

Figure 5. DSC thermograms (a) and XRD curves (b) of the pure TanIIA powder (A), PM (B), TanIIA@MSNs (C), TanIIA@LB-MSNs (D) and TanIIA@ Bio-LB-MSNs (E).

Figure 6. Confocal laser scanning microscopy (CLSM) images (a) and Flow cytometry (b) of Caco-2 cells incubated with Cou-6@MSNs, Cou-6@LB-MSNs, Cou-6@Bio-LB-MSNs or free biotin solution pretreated Cou-6@Bio-LB-MSNs for 1.5 h at 37 °C. (Scale bars for CLSM images are 25 μm. From left to right, cell nuclei stained by Hoechst 33258 (blue), nanoparticles labelled by Cou-6 (green) and the merge of the two images. The cells without any treatment were used as control).

Figure 7. In vitro release profiles of the pure TanIIA powder, TanIIA@MSNs, TanIIA@LB-MSNs and TanIIA@Bio-LB-MSNs. (n = 3).

Table 3. The P_app of TanIIA solution, TanIIA@MSNs, TanIIA@LB-MSNs and TanIIA@Bio-LB-MSNs in jejunum (n = 3).

Sample	Papp /×10^−5(cm/s)
TanIIA solution	8.90 ± 0.48
TanIIA@MSNs	13.71 ± 3.17
TanIIA@LB-MSNs	16.85 ± 4.06*
TanIIA@Bio-LB-MSNs	22.60 ± 0.31*

*p ≤ .05 compared with the pure TanIIA powder.

Figure 8. Plasma concentration–time profiles of the pure TanIIA powder, TanIIA@MSNs, TanIIA@LB-MSNs and TanIIA@Bio-LB-MSNs following oral administration in SD rats at a dose of 35 mg/kg (n = 5).

Table 4. Main pharmacokinetic parameters of the pure TanIIA powder, TanIIA@MSNs, TanIIA@LB-MSNs and TanIIA@Bio-LB-MSNs after oral administration to SD rats at a dose of 35 mg·kg⁻¹ (n = 5).

Pharmacokinetic parameters	TanIIA	TanIIA@MSNs	TanIIA @LB-MSNs	TanIIA @Bio-LB-MSNs
Cmax (ng·ml^−1)	120.5 ± 31.3	323.7 ± 54.1*	315.8 ± 37.4*	1152.0 ± 88.0*
Tmax (h)	3.4 ± 0.5	2.8 ± 1.9	3.0 ± 0.0	3.0 ± 0.0
t1/2 (h)	9.1 ± 3.3	5.9 ± 1.2*	7.6 ± 0.8	5.5 ± 1.3*
AUC0–∞ (ng·h·ml^−1)	1512.4 ± 251.9	2856.8 ± 705.1*	2259.6 ± 91.4*	5316.2 ± 329.1*

C_max: peak plasma concentration; T_max: time to reach the peak plasma concentration; t_1/2: elimination half-life; AUC_0–∞: area under the plasma concentration–time curve

*p ≤ .05 compared with the pure TanIIA powder.

Figure 9. Growth inhibition rate on NB₄ cells treated with different samples for 24 h measured by CCK-8 assay.