Assessment to the Antifungal Effects in vitro and the Ocular Pharmacokinetics of Solid-Lipid Nanoparticle in Rabbits

Figures & data

Table 1 Various Characterizations of the E-SLNs

Batch	Mean Diameter (nm)	Polydispersity Index	Zeta Potential	%EE	% SLN
E-SLNs	19.05 ± 0.28	0.21 ± 0.01	−2.20 ± 0.10	94.18 ± 1.86	99.35 ± 0.16

Note: All values are expressed as the means ± SD (n = 3).

Abbreviations: % EE, percentage entrapment efficiency; % SLN, proportion of ECZ incorporated into SLNs.

Figure 1 (A) Transmission electron microphotograph of E-SLNs. Bar = 100 nm. (B) Particle size distribution of E-SLNs.

Figure 2 In vitro release profiles of E-SLNs (pH 7.4 artificial tear solution was used as the dialysis medium, n = 3, mean ± SD).

Table 2 Mathematical Models of Regression for the in vitro Release Profiles of E-SLNs

Kinetic Model	Equation	r^2
Zero order	y=0.93x+5.85	0.9744
First order	y=114.33-e^4.74−0.015x	0.9830
Higuchi	y=8.57(x^(1/2))+1	0.9900

Figure 3 DSC thermograms of tripalmitin (TM), econazole (ECZ), E-SLNs and a physical mixture of ECZ and TM.

Table 3 Corneal Permeation Parameters of the ECZ from E-SLNs and E-Susp and the Hydration Rates

Group	Papp*10^5 (cm·s^−1)	Jss*10^3 (μg·s^−1cm)	Hydration Rate (%)
E-SLNs	7.13 ± 0.05	4.28 ± 0.03	76.25 ± 2.29
E-Susp	1.96 ± 0.23	1.29 ± 0.15	89.13 ± 1.15

Note: All values are expressed as means ± SD (n = 3).

Table 4 Comparative Study of the Antifungal Activity of E-SLNs and E-Susp Against A.Fusarium

Formulation	Mean of Diameter of Zone of Inhibition (mm)	MIC50 (μg/mL)	MIC90 (μg/mL)
E-SLNs	25 ± 1	0.37	0.89
E-Susp	18 ± 1	0.90	1.56

Note: All values are expressed as the means ± SD (n = 3).

Abbreviations: MIC₅₀, minimal inhibitory concentration for 50% of the strains tested; MIC₉₀, minimal inhibitory concentration for 90% of the strains tested.

Figure 4 Microbiological studies against A.Fusarium by the agar diffusion method for 48 h.

Figure 5 Representative images of the in vivo rabbit ocular irritation test. (A) E-SLNs, (B) Saline.

Table 5 Ocular Pharmacokinetic Parameters of E-SLNs and E-Susp in the Tear Liquid and Cornea After the Administration of Different Formulations

Pharmacokinetic Parameters		Formulations
		E-SLNs	E-Susp
Tear film	Tmax(min)	5	5
	Cmax(mg/L)	597.64±309.77	1570.54±208.21^##
	MRT(0–t)	50.25	31.74
	AUC(0–180min) (mg/L*min)	13,957.45	30,921.78
Cornea	Tmax (min)	5	5
	Cmax (mg/L)	33.15±6.82**	8.85±3.42
	MRT(0–t)	43.99	35.29
	AUC(0–180min) (mg/L*min)	1539.73	536.1

Notes: All values are expressed as the means ± SD (n = 3); C_max the maximum concentration of drug in eye tissue, T_max time required to reach the maximum eye tissue concentration, AUC the area under eye tissue concentration-time curve from 0 to 180 min, MRT mean residue time. **Considered significant compared to E-Susp (p< 0.01). ^##Considered significant compared to E-SLNs (p< 0.01).

Figure 6 Pharmacokinetics studies in rabbit eyes after a single administration of either formulation. The ECZ concentration-time profiles in the (A) Tear film and (B) Corneas of rabbits. The drugs were E-SLNs and E-Susp at a single dose of 50 μL. Values are given as the mean ± SD (n=6). **Significantly different (p < 0.01) from the E-Susp group. ^##Significantly different (p < 0.01) from the E-SLN group.