Lung-targeting drug delivery system of baicalin-loaded nanoliposomes: development, biodistribution in rabbits, and pharmacodynamics in nude mice bearing orthotopic human lung cancer

Figures & data

Table 1 The characterization of three batch samples of baicalin-loaded nanoliposomes

Batch	Mean size (nm)	PDI	EE (%)	Yield (%)
1	129.7±13.5	0.20±0.02	82.6±1.09	91.5
2	137.9±10.5	0.18±0.02	83.8±1.35	90.2
3	129.9±8.8	0.20±0.02	81.9±1.29	89.7

Note: Data presented as mean ± standard deviation.

Abbreviations: PDI, polydispersity index; EE, entrapment efficiency.

Figure 1 Cumulative percent drug release from baicalin-loaded nanoliposomes and its solution (n=3).

Table 2 The stability of baicalin-loaded nanoliposomes (mean ± SD, n=3)

Time (months)	0	1	2	3	6	9	12
EE (%)	82.8±1.24	82.6±1.28	82.5±1.26	82.3±1.52	81.9±1.79	81.5±2.02	81.1±1.88
Size (nm)	131.7±11.8	132.9±10.7	133.5±13.6	134.0±9.2	137.1±12.3	138.5±10.4	140.3±13.2

Abbreviations: SD, standard deviation; EE, entrapment efficiency.

Figure 2 Hemolysis of erythrocytes by various drug concentrations of baicalin-loaded nanoliposomes (n=3).

Figure 3 Distribution in rabbit tissues after intravenous administration of baicalin solution ($\overline{x}\pm \text{SD}$, n=5; plasma: μg/mL, tissues: μg/g).

Abbreviation: SD, standard deviation.

Figure 4 Distribution in rabbit tissues after intravenous administration of baicalin liposomes ($\overline{x}\pm \text{SD}$, n=5; plasma: μg/mL, tissues: μg/g).

Abbreviation: SD, standard deviation.

Table 3 The lung-targeting parameters of baicalin liposomal formulation and its solution after intravenous administration in rabbita

Biosample	AUC (µg⋅h/mL or µg⋅h/g)b		Re	Te		Ratio of Te	Ce
	Liposomes	Solution		Liposomes	Solution
Plasma	2.42	7.07	0.342	65.045	4.603	14.131	0.308
Heart	22.10	15.23	1.451	7.123	2.137	3.333	0.789
Liver	82.57	32.31	2.556	1.906	1.007	1.893	1.103
Spleen	69.47	48.22	1.441	2.266	0.675	3.357	1.335
Lung	157.41	32.54	4.837	1.000	1.000	1.000	2.789
Kidney	62.31	44.68	1.395	2.526	0.728	3.470	0.729
Stomach	34.75	42.50	0.818	4.530	0.766	5.914	0.537
Brain	9.84	10.72	0.918	15.997	3.035	5.271	0.564

Notes:

a These values are arithmetic means, n=5.

b Unit of AUC in plasma was μg⋅h/mL and unit of AUC in tissue was μg⋅h/g. R_e, intake rate; T_e, targeting efficacy; C_e, peak concentration ratio.

Abbreviation: AUC, area under the curve.

Figure 5 The pathological sections of lung at 1 (A), 4 (B), and 7 days (C) after intravenous administration of baicalin-loaded nanoliposomes and saline (D) as the control. Magnification ×200.

Figure 6 Pharmacodynamics in nude mice bearing orthotopic human lung cancer intravenously administered with baicalin-loaded nanoliposomes.

Notes: (A) Total tumor weight of each group when the mice was naturally scarified. (B) Increased tumor weight daily of each group. (C) Survival rate study.