Antifungal activity of osthol in vitro and enhancement in vivo through Eudragit S100 nanocarriers

Figures & data

Figure 1. Struction of Osthol (Ost).

Figure 2. Agar disk diffusion assay of FLC combined with Ost against C.albicans 103. Panels A and C show plain agar plates, and panel B shows an agar plate containing 64 μg/ml of FLC. Panel D describes the images for panels A and B, and panel E describes the image for panel C.

Table 1. Interaction of FLC and Ost against 11 clinical isolates of C. albicans resistant to FLC by MIC₈₀s of checkerboard microdilution assay.

	MIC80 (μg/ml) alone		MIC80(μg/ml) in combination
Clinical Isolates	FLC	Ost	FLC	Ost	FIC index for combination	Mode of Interaction
953	64	32	2	4	0.156	Syn
J35	64	32	1	8	0.266	Syn
32	64	64	2	4	0.094	Syn
904	>64	>64	2	4	0.047	Syn
557	>64	64	2	2	0.047	Syn
842	>64	64	2	2	0.047	Syn
901	>64	16	2	4	0.266	Syn
100	>64	32	4	4	0.141	Syn
103	>64	64	4	4	0.078	Syn
J28	>64	64	8	8	0.187	Syn
J5	>64	64	2	8	0.156	Syn
ATCC90028	0.25	8	0.0625	1	0.3725	Syn

Figure 3. The characteristics of Ost-S100-NP. (A) Particle size distributions of Ost-S100-NP. (B) X-ray diffraction of (a) Ost (b) S100 (c) Poloxamer 188 (d) physical mixture of Ost、Eudragit S100 and Poloxamer 188 (e) Ost-S100-NP. (C) DSC spectra of (a) Ost (b) S100 (c) P188 (d) physical mixture of Ost、S100 and P188 (e) Ost-S100-NP. (D) Appearance of Ost-S100-NP under electric microscope (× 50,000).

Figure 4. Blood concentration of profile of Ost after oral Administration of Ost-suspension(■) and Ost-S100-NP(▴) to fasted rats at a dose of 25 mg/kg (n = 8).

Table 2. The Main Pharameters after Oral Administration of Ost-suspension and Ost-S100-NPs in rats. Mean ± SE (n = 8).

Parameters	Units	Ost-suspension	Ost-S100-NP
Cmax	μg·ml^−1	1.87 ± 0.24	3.15 ± 0.29^##
Tpeak	h	2.25 ± 0.21	4.21 ± 0.25^##
ka	h^−1	1.25 ± 0.16	0.44 ± 0.09^##
k10	h^−1	0.43 ± 0.02	0.45 ± 0.02^#
AUC	μg·h·ml^−1	55.47 ± 3.33	93.58 ± 4.85^##
CL	mg·kg^−1·h^−1/ μg·ml^−1	0.45 ± 0.02	0.27 ± 0.01^##
MRT	h	22.10 ± 0.87	23.48 ± 0.64^##
Fr(%)		—	168.7%

Notes.

# P < 0.05 vs. Ost-suspension;

## P < 0.01 vs. Ost-suspension.

C_max: maximum concentration; T_peak: time to reach C_max; k_a: the absorption constant from gastrointestinal tract to central compartment; k₁₀: elimination constant of the central compartment; AUC:area under concentration curve; CL: clearance; MRT: mean retention time; Relative bioavailability: Fr % = ( AUC_Ost-S100-NP / AUC_{Ost-suspension}) × 100%

Figure 5. Kaplan-Meier survival curves of C. albicans 103 infecting mice treated with physiologic saline (1(1) $Yield(\%)=\frac{c_1 \times v}{w_c} \times 100\%$(1) ), FLC single (2(2) $EP(\%)=\frac{(c_1-c_2) \times v}{c_1 \times v} \times 100\%$(2) ), Ost-S100-NP single (3(3) $LD(\%)=\frac{(c_1-c_2) \times v}{w_z} \times 100\%$(3) ), Ost-suspensions single (4), Ost-S100-NP combinate FLC (5), and Ost-suspensions combinate FLC (6) respectively.