Development of lipid nanoparticles for a histone deacetylases inhibitor as a promising anticancer therapeutic

Figures & data

Figure 1. Drug solubility in various vehicles. (1) Capryol™ PGMC, (2) Capryol™ 90, (3) Lauroglycol-FCC, (4) castor oil, (5) Labrafil M1944CS, (6) Labrafil M2125 CS, and (7) Peceol. Data represent the mean ± standard deviation (n = 3).

Figure 2. Effect of compositions on formulation parameters: particle size, polydispersity index (PDI), and zeta potential (ZP). (A) Liquid lipid concentration, (B) lipid concentration, (C) Tween 80 concentration, (D) drug concentration. Data are expressed as the mean ± standard deviation (n = 3).

Table 1. Compositions of VRS-NLCs.

		Compositions
Formulations	Precirol	Capryol 90	Lecithin	Tween 80	VRS	Water (mL)
1	5	0.5	0.5	1.5	0	10
2	4.5	1.0	0.5	1.5	0	10
3	4	1.5	0.5	1.5	0	10
4	3.5	2.0	0.5	1.5	0	10
5	3	2.5	0.5	1.5	0	10
6	3.6	0.8	0.4	1.5	0	10
7	4.5	1.0	0.5	1.5	0	10
8	5.4	1.2	0.6	1.5	0	10
9	4.5	1.0	0.5	2.5	0	10
10	4.5	1.0	0.5	2.0	0	10
11	4.5	1.0	0.5	1.5	0	10
12	4.5	1.0	0.5	1.0	0	10
13	4.5	1.0	0.5	1.5	0.05	10
14	4.5	1.0	0.5	1.5	0.10	10
15	4.5	1.0	0.5	1.5	0.15	10

Unit for all components: % m/v.

Figure 3. Drug entrapment efficiency and loading capacity.Data are expressed as the mean ± standard deviation (n = 3).

Figure 4. TEM image of VRS-NLCs.

Figure 5. (A) Differential scanning calorimetric (DSC) thermograms and (B) X-ray diffraction (XRD) patterns of solid lipid, free VRS, and VRS-NLCs.

Figure 6. In vitro drug release from VRS-NLCs under different conditions: pH 1.2 (Δ) and pH 6.8 (•).

Figure 7. Intracellular uptake of NLCs in (A) SCC-7 cell, and (B) MCF-7 cells. NLCs contain NBD-PC (green) as a fluorescent probe. The LysoTracker Red stained for lysosome (red).

Figure 8. Cell viability following exposure of MCF-7, A549, and SCC-7 cells to blank NLCs, free VRS, and VRS-NLCs for 24 h. Data are expressed as the mean ± standard deviation (n = 8).

Figure 9. Plasma concentration-time profile of VRS after oral administration at a dose of 30 mg/kg of free VRS (□) or VRS-NLCs (▪). Data are expressed as the mean ± standard deviation (n = 4).

Table 2. Pharmacokinetic parameters of VRS in rats after oral administration of free VRS and VRS-NLCs at a dose of 30 mg/kg.

Parameter	Free VRS	VRS-NLCs
Tmax (h)	1	4*
Cmax (µg/mL)	8.95 ± 0.12	9.76 ± 0.91*
t1/2 (h)	2.27 ± 1.21	11.99 ± 0.55*
AUC0-∞ (µg.h/mL)	27.03 ± 3.25	118.16 ± 17.35*
MRT (h)	3.47 ± 1.68	15.28 ± 3.36*

Data are expressed as the mean ± SD (n = 4).

*p < 0.05, compared to the free drug.