Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles

Figures & data

Figure 1 (A) TEM image of HSYA nanoparticles, (B) FERTEM image of HSYA nanoparticles, and (C) Size distribution of freshly prepared HSYA nanoparticles. Abbreviations: FER, freeze-etching replication; HSYA, hydroxysafflor yellow A; TEM, transmission electron microscopy.

Table 1 Pharmacokinetic parameters after intravenous or oral administration of HSYA formulations to rats

	Intravenous HSYA	Oral
		HSYA solution	HSYA-NPs
Tmax (min)	5	45 ± 15	90.00 ± 51.96
Cmax(μg/mL)	56.51 ± 29.05	0.33 ± 0.05	4.80 ± 2.77*
AUC0–12 (μg minute/mL)	2,477.68 ± 221.11	39.92 ± 6.20	931.53 ± 406.34**
MRT (minute)	77.47 ± 6.74	227.20 ± 12.29	311.12 ± 26.52**
Thalf (minute)	353.32 ± 64.29	407.61 ± 241.36	579.97 ± 216.47
Frel (%)	–	100	2,333
Fab (%)	100	1.61	38

Notes: The values represent mean ± standard deviation (n = 3)

** P<0.01

** P<0.05 compared to control.

Abbreviations: AUC, areas under the concentration time curve; C_max, maximum plasma concentration; F_rel, relative bioavailability; F_ab, absolute bioavailability; HSYA, hydroxysafflor yellow A; MRT, mean retention time; NPs, nanoparticles; T_half, halflife; T_max, time to maximum plasma concentration.

Figure 2 HSYA release from nanoparticles in double-distilled water at 4°C (n = 3).

Note:Figure 2B is an enlarged version of Figure 2A.

Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.

Figure 3 (A) Cytotoxicity of blank nanoparticles on Caco-2 cells after incubation for 2 hours; (B) Cellular integrity studies of incubation with nanoparticles and removal of nanoparticles (n = 3).

Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle; TEER, transepithelial electrical resistance.

Figure 4 (A) HSYA solution and HSYA nanoparticle uptake by Caco-2 monolayers after incubation for 2 hours; (B) HSYA transport across Caco-2 cells (surface area of monolayer = 1.12 cm²); (C) Endocytotic inhibitor studies on Caco-2 cells of HSYA-NPs.

Notes: *P<0.05; **P<0.01, compared to control.

Abbreviations: CSA, cyclosporin A; HSYA, hydroxysafflor yellow A; Methyl-β-CD, methyl-β-cyclodextrin; NP, nanoparticle; T, time.

Figure 5 (A) ZO-1 staining in control cell layers not subjected to HSYA nanoparticles; (B) ZO-1 staining in cells incubated with 10-fold dilution HSYA-NPs for 2 hours at 37°C.

Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.

Figure 6 (A) Plasma concentration-time profiles of HSYA after intravenous administration of HSYA solution, (B) oral administration of HSYA solution, and (C) HSYA-NPs to rats at a dose of 25 mg/kg.

Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.