Formulation, characterization, and in vitro/vivo studies of aclacinomycin A-loaded solid lipid nanoparticles

Figures & data

Figure 1. The structure of ACM (A) and Quercetin (B, internal standard).

Figure 2. Transmission electron microscope photograph of ACM-SLNs. × 3000.

Figure 3. DSC analyses of the samples: (A) ACM, (B) blank SLNs, (C) physical mixture of ACM and blank SLNs, (D) ACM-SLNs.

Figure 4. X-ray diffraction spectra of (A) ACM, (B) physical mixture of ACM and blank SLNs, (C) blank SLNs, and (D) ACM-SLNs.

Figure 5. In vitro release profiles of ACM-SLNs from three batches. Release experiments were carried out in phosphate buffer solution (PBS) (pH 7.4), at 37 ± 0.5 °C. Each point represents the mean value of three different experiments ± SD ⋄, free ACM; △, ACM-SLNs; *p < 0.05 free ACM versus ACM-SLNs.

Table 1. Correlation coefficients for kinetic analysis of release data for ACM-SLNs.

	Correlation coefficient (r)
Formulation	Zero order	First order	Higuchi	Weibull
ACM-SLNs	0.9612	0.9733	0.9993	0.9826

Figure 6. Mean plasma concentration–time profiles of ACM after i.v. administration of a single 10 mg/kg dose of free ACM and ACM-SLNs to rats. The values are expressed as mean ± SD (n = 6).

Table 2. Pharmacokinetic parameters of the two formulations.

	Formulations
Parameter	Injection	SLNs
t1/2α (h)	0.18 ± 0.3	0.94 ± 0.5*
t1/2β (h)	2.6 ± 1.1	12.9 ± 2.8*
Cmax (ng/mL)	3950.5 ± 334.3	2019.3 ± 232.5*
AUC0 − t (ng·h/mL)	3015.6 ± 318.1	15 376.2 ± 1021.4*
AUC0 − ∞ (ng·h/mL)	4231.7 ± 353.6	20 542.6 ± 1207.9*
MRT (h)	11.2 ± 3.1	23.9 ± 4.3*
CL (L/h)	27.7 ± 4.7	14.8 ± 3.1*

C_max, maximum plasma concentration; AUC_0 − t, area under the concentration–time curve from time 0 to the last measurable concentration; AUC_{0 − ∞}, area under the concentration–time curve extrapolated to infinity; MRT, mean residence time; CL, plasma clearance.

*p < 0.05: ACM-SLNs versus ACM injection.

Figure 7. Distribution in tissue in rats after following i.v. administration of a single 10 mg/kg dose of ACM injection tissues (ng/g) (each point represents the mean ± SD of six rats).

Figure 8. Distribution in tissue in rats after following i.v. administration of a single 10 mg/kg dose of ACM-SLNs tissues (ng/g) (each point represents the mean ± SD of six rats).

Table 3. The AUC_{0 − 24 h} of ACM in tissues after i.v. administration of injection and SLNs to rats.

Formulation	Heart	Liver	Spleen	Lung	Kidney
ACM injection (ng·h/g)	2612.3 ± 221.4	1920.5 ± 132.5	2522.5 ± 232.7	2658.2 ± 224.3	3987.5 ± 365.9
ACM-SLNs (ng·h/g)	317.1 ± 29.6	4002.1 ± 378.7	905.2 ± 101.2	632.5 ± 73.8	373.9 ± 43.8
Ratio^a	0.12*	2.08*	0.36*	0.24*	0.09*

^aThe ratio was AUC (ACM-SLNs) /AUC (ACM injection).

*p < 0.05: ACM-SLNs versus ACM injection.

Figure 9. Histopathological studies of liver, spleen, and kidney. (A) Free ACM and (B) ACM-SLNs.