Targeted delivery of an anti-cancer agent via steroid coupled liposomes

Figures & data

Figure 1.  Synthesis of testosterone-lipid conjugate (T-DSPE).

Figure 2.  TEM photograph of T-DSPE coupled liposomes (80,000).

Table 1.  Characterization of uncoupled and testosterone (T-DSPE) coupled liposome formulations.

S. No.	Formulations	Vesicle size (nm)	Polydispersity index	Entrapment efficiency	Drug release in 24 h
1	Uncoupled liposomes	188 ± 16	0.203 ± 0.043	29.4 ± 1.34%	87.2 ± 3.54%
2	T-DSPE coupled liposomes	232 ± 21	0.181 ± 0.064	27.3 ± 1.82%	79.50 ± 2.81%

Figure 3.  Fluorescent uptake after 1 h administration of 6-CF bearing uncoupled liposomes (alphabetical) and T-DSPE coupled liposomes (alphabetical artistic) in various androgen target organs. (A) Liver, (B) Prostate, (C) Testis, (D) Brain, (E) Spleen, (F) Kidney. The photographs clearly reveal that after administration of T-DSPE coupled liposomes the fluorescence of testosterone targeted organs is higher as compared to uncoupled liposomes, i.e. liver, prostate, testis, and brain, while non-target organs, i.e. spleen and kidney, show lesser fluorescence after administration of T-DSPE liposomes. It is clear that T-DSPE liposomes have better selectivity towards ARs targeted organs.

Figure 4.  Infra red spectrum of testosterone-DSPE lipid (T-DSPE) conjugate.

Figure 5.  In vitro drug release of various liposomal formulations in PBS (pH 7.4) (n = 3).

Figure 6.  Plasma drug level after administration of 5-FU drug solution and various liposomal formulations (n = 3).

Table 2.  Drug recovered in various organs after various time intervals.

Formulation	Drug 5-FU recovered (μg/g)
	Organs	1 h	2 h	4 h	8 h	24 h
5-FU drug solution	Prostate	1.51 ± 0.22	1.94 ± 0.02	2.14 ± 0.4	0.57 ± 0.16	ND
	Brain	1.04 ± 0.21	1.44 ± 0.72	0.68 ± 0.02	ND	ND
	Testis	0.87 ± 0.62	1.86 ± 1.01	1.52 ± 0.52	ND	ND
	Liver	3.3 ± 0.48	4.8 ± 1.21	3.2 ± 1.02	ND	ND
	Kidney	3.62 ± 0.43	3.32 ± 0.24	2.82 ± 0.46	1.02 ± 0.46	ND
	Spleen	2.18 ± 0.46	2.12 ± 0.12	1.50 ± 0.82	ND	ND
5-FU bearing uncoupled liposomes	Prostate	2.68 ± 0.34	3.24 ± 0.02	3.66 ± 0.72	3.74 ± 0.32	1.64 ± 0.36
	Brain	1.43 ± 0.32	2.36 ± 0.23	2.01 ± 0.52	2.23 ± 0.16	1.21 ± 0.22
	Testis	1.22 ± 0.12	2.21 ± 0.64	3.20 ± 0.16	2.03 ± 0.26	1.28 ± 0.16
	Liver	6.20 ± 0.76	6.32 ± 1.26	4.72 ± 1.85	2.32 ± 0.16	1.33 ± 0.16
	Kidney	2.02 ± 0.16	2.52 ± 0.36	1.4 ± 1.02	1.52 ± 0.08	1.12 ± 0.12
	Spleen	2.43 ± 0.42	2.55 ± 0.14	3.20 ± 0.06	2.62 ± 0.12	0.92 ± 0.11
5-FU bearing T-DSPE coupled liposomes	Prostate	3.72 ± 0.24	7.78 ± 1.21	12.74 ± 0.34	8.48 ± 1.04	3.08 ± 0.23
	Brain	2.82 ± 0.42	4.40 ± 1.01	5.84 ± 0.46	4.12 ± 0.42	2.18 ± 0.34
	Testis	1.96 ± 0.31	4.53 ± 0.14	7.78 ± 0.32	5.22 ± 0.14	2.28 ± 0.32
	Liver	5.78 ± 1.24	7.24 ± 1.26	8.72 ± 0.34	6.08 ± 0.74	2.43 ± 1.34
	Kidney	2.23 ± 0.42	2.88 ± 0.32	1.28 ± 0.31	1.91 ± 0.40	1.72 ± 0.24
	Spleen	2.28 ± 0.14	2.71 ± 1.64	3.38 ± 0.74	2.78 ± 0.31	1.18 ± 0.26

Note: Values are mean ± SD; n = 3; p < 0.05. All the values at respective time points for each formulation were used for statistical comparisons.

Figure 7.  Accumulation of 5-FU in prostate tissues after administration of 5-FU drug solution, 5-FU bearing uncoupled liposomes and T-DSPE coupled liposomes (n = 3).