RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer

Figures & data

Figure 1 Scanning electron micrograph of RGD-ACM liposomes.

Notes: Magnification 50,000×. (A) RGD-ACM liposomes and (B) non-modified ACM liposomes.
Abbreviations: ACM, aclacinomycin A; RGD, arginine-glycine-aspartic acid.

Figure 2 In vitro release of ACM-loaded liposomes in phosphate-buffered saline (pH 7.4, n=3).

Notes: Gray line indicates free ACM; light blue line indicates ACM liposomes, red line indicates RGD-ACM liposomes.
Abbreviations: ACM, aclacinomycin A; RGD, arginine-glycine-aspartic acid.

Figure 3 The sample did not aggregate and still had the appearance of a milky white colloidal solution after being dissolved in phosphate-buffered saline (pH 7.4) and kept at 4°C for (A) one month and (B) two months.

Table 1 Pharmacokinetic parameters of the two formulations

Parameter	Formulations
	RGD-ACM liposomes	ACM liposomes
t1/2 (hours)	1.45±0.54	1.21±0.41
Cmax (ng/mL)	4,532.4±267.4	3,425.6±324.9*
AUC0–t (ng⋅h/mL)	11,835.6±1,023.7	7,889.5±872.5*
AUC0–∞ (ng⋅h/mL)	14,328.3±1,121.5	9,317.2±917.1*
MRT (hours)	1.21±0.58	0.58±0.32
CL (L/hour)	32.76±5.42	41.27±2.82

Note:

* P<0.05, ACM liposomes versus RGD-ACM liposomes.

Abbreviations: ACM, aclacinomycin A; AUC, area under the concentration time curve; RGD, arginine-glycine-aspartic acid; CL, clearance; MRT, mean residence time; C_max, peak plasma concentration; t_1/2, biological half-life.

Figure 4 Mean plasma ACM concentration in rats after intravenous administration (8 mg/kg) of the two formulations (n=6). The blue line indicates RGD-ACM liposomes and the red line indicates ACM liposomes.

Abbreviations: ACM, aclacinomycin A; RGD, arginine-glycine-aspartic acid.

Table 2 Effect of RGD-ACM liposomes and ACM liposomes on A549 cells in nude mice

Formulation	TV (mm^3)		Tumor weight (g)	R	IR (%)
	d1	d10
Saline group	136±32	745±237	0.719±0.261	6.12±1.52
ACM liposomes	133±29	254±126a	0.226±0.125a	1.37±0.74a	77.6%
RGD-ACM liposomes	132±33	119±32a,b	0.128±0.054a,b	0.96±0.34a,b	84.3%

Notes:

a P<0.01 versus saline group;

b P<0.05 versus ACM liposome group.

Abbreviations: ACM, aclacinomycin A; RGD, arginine-glycine-aspartic acid; TV, tumor volume; R, relative tumor volume; T/C, tumor inhibitory ratio; IR, inhibited rate.

Figure 5 Changes in tumor volume in nude mice transplanted with a human adenocarcinoma (A549) cell line on day 10.

Notes: (A) Saline, (B) ACM liposomes, and (C) RGD-ACM liposomes.
Abbreviations: ACM, aclacinomycin A; RGD, arginine-glycine-aspartic acid.