Amsacrine analog-loaded solid lipid nanoparticle to resolve insolubility for injection delivery: characterization and pharmacokinetics

Figures & data

Figure 1 The chemical structure of (A) amsacrine and (B) amsacrine analog.

Table 1 Characterization of amsacrine analog–loaded solid lipid nanoparticles (SLNs) in terms of the particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency, and stability changes following storage at room temperature (25°C) for 1 month

Formulation	Original	After 1 month
Particle diameter (nm)	36.7±0.6	40.10±7.1
PDI	0.37±0.04	0.44±0.12
Zeta potential (mV)	34.5±4.7	37.4±3.2
Entrapment efficiency (%)	99.58±0.09	98.75±0.10

Note: Each value represents mean ± SD (n=3).

Abbreviation: SD, standard deviation.

Figure 2 Transmission electron microscopic micrograph of amsacrine analog-loaded solid lipid nanoparticle (SLN) (original magnification ×100 K).

Figure 3 In vitro accumulative amount release versus time profiles of amsacrine analog from solid lipid nanoparticle (SLN).

Note: Each value represents mean ± SD (n=3).
Abbreviation: SD, standard deviation.

Table 2 Average pharmacokinetic parameters after intravenous administration of amsacrine analog solution and amsacrine analog-loaded SLN to mice with a dose of 8.4 mg/kg for 4 hours

Parameters	Amsacrine analog solution	Amsacrine analog-loaded SLN
t1/2α (hour)	0.1955±0.002	0.3469±0.007
t1/2β (hour)	1.4375±0.067	0.8026±0.087
Cl (L/h/kg)	20.3287±1.254	44.0903±3.501
Vdss (L/kg)	23.1743±1.563	34.0650±4.184
AUC0→∞ (h·μg/mL)	0.4132±0.003	0.1905±0.004
MRT (hour)	1.1400±0.006	0.7726±0.009

Note: Each value represents mean ± SD (n=6).

Abbreviations: SLN, solid lipid nanoparticle; t_1/2α, half-life of the distribution phase; t_1/2β, half-life of the elimination phase; Cl, clearance; Vdss, steady-state volume of distribution; AUC, area under tissue concentration–time curve; MRT, mean residence; SD, standard deviation.

Table 3 AUC and mean residence time of amsacrine analog in various organs upon administration of amsacrine analog with or without SLN

Parameters	Formulations	Organs
		Heart	Liver	Spleen	Lung	Kidney	Brain	Intestine
AUC0−∞ (h·μg/mL)	Amsacrine analog solution	0.3143	0.6913	0.2117	0.5915	1.0669	0.4015	0.4222
	Amsacrine analog-loaded SLN	0.2164	2.3000	1.7113	71.1698	1.0826	0.0588	0.0636
MRT (hour)	Amsacrine analog solution	0.6883	0.7727	0.9841	0.7681	0.7991	0.8547	0.8785
	Amsacrine analog-loaded SLN	0.8075	1.2507	1.2821	2.7101	1.2685	0.6088	0.6572
	Fr	0.6885	3.3270	8.0836	120.3208	1.0147	0.1465	0.1506

Note: Fr = AUC_SLN/AUCsolution.

Abbreviations: SLN, solid lipid nanoparticle; Fr, relative bioavailability; AUC, area under tissue concentration–time curve; MRT, mean residence time.

Figure 4 Concentration–time profiles in organs after intravenous administration of amsacrine analog with or without SLN at dose 8.4 mg/kg in mice.

Note: Each value represents mean ± SD (n=6).
Abbreviations: SLN, solid lipid nanoparticle; SD, standard deviation.

Figure 5 In vivo biodistribution images of IR-780-loaded SLN in mice by using IVIS technique. The left side is a bright field; the right side is the intensity of IR-780 in various organs. The color bar presents the signal efficiency of the fluorescence emission coming out from the violet.

Abbreviations: SLN, solid lipid nanoparticle; Min, minimum; Max, maximum; IVIS, noninvasion in vivo imaging system.