Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats

Figures & data

Table 1 Physicochemical characterizations of PNS formulations (n = 3)

Type	Median particle size diameter (nm)	Zeta potential (mV)	EE%
			R1	Rb1	Rg1	RSD
PNS-NP	117.1 ± 9.7	−18.7 ± 0.44	31.7 ± 1.4	72.4 ± 1.2	15.2 ± 2.0	74.0%
PNS-LP	147.0 ± 12.4	−22.5 ± 0.39	42.8 ± 1.8	65.6 ± 1.9	28.3 ± 1.1	41.3%
PNS-HLV	337.8 ± 40.2	−44.7 ± 0.51	57.5 ± 1.1	83.1 ± 1.7	40.5 ± 1.8	35.5%

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1; RSD, relative standard deviation.

Figure 1 Transmission electron microscopy images of (A) PNS-NP, (B) PNS-LP, and (C) PNS-HLV.

Note: Bar is 500 nm.

Abbreviations: PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles.

Table 2 Storage stability of PNS formulations at 4°C

Time (mon)	EE (R1, %)			EE (Rb1, %)			EE (Rg1, %)			Median particle size diameter (nm)
	PNS-NP	PNS-LP	PNS-HLV	PNS-NP	PNS-LP	PNS-HLV	PNS-NP	PNS-LP	PNS-HLV	PNS-NP	PNS-LP	PNS-HLV
0	31.7 ± 1.4	42.8 ± 1.8	57.5 ± 1.1	72.4 ± 1.2	65.6 ± 1.9	83.1 ± 1.7	15.2 ± 2.0	28.3 ± 1.1	40.5 ± 1.8	117.1 ± 9.7	147.0 ± 12.4	337.8 ± 40.2
1	31.5 ± 1.2	40.9 ± 1.7	57.7 ± 1.5	71.8 ± 1.5	64.7 ± 1.7	82.8 ± 1.1	12.9 ± 1.8	26.9 ± 1.4	39.5 ± 1.5	121.6 ± 7.6	151.9 ± 23.5	355.4 ± 29.5
3	29.4 ± 1.2	39.3 ± 1.8	56.8 ± 1.1	68.2 ± 2.2	63.9 ± 1.4	82.4 ± 1.8	11.7 ± 1.3	25.4 ± 1.9	39.1 ± 1.9	123.1 ± 14.8	169 ± 16.7	348 ± 30.7
6	29.8 ± 1.3	39.0 ± 1.6	56.9 ± 1.3	69.3 ± 1.8	62.6 ± 1.8	82.5 ± 1.6	9.8 ± 2.2	23.2 ± 1.2	40.9 ± 1.3	137.0 ± 42.9	174.0 ± 6.6	350.1 ± 30.4
12	28.4 ± 1.9	38.7 ± 2.1	56.2 ± 1.8	69.7 ± 1.3	61.5 ± 2.2	81.7 ± 1.5	8.7 ± 1.6	22.8 ± 1.7	40.4 ± 2.0	140.1 ± 55.9	185.1 ± 29.9	359.7 ± 28.1

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1.

Figure 2 Cumulative percentage release profiles of R1, Rb1, and Rg1 from PNS preparations at pH = 7.4 (n = 3).

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1.

Figure 3 Cumulative percentage release profiles of R1, Rb1, and Rg1 from PNS preparations at pH = 6.8 (n = 3).

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1.

Figure 4 Cumulative percentage release profiles of R1, Rb1, and Rg1 from PNS preparations at pH = 2 (n = 3).

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1.

Figure 5 Effect of different PNS preparations on brain water content of rats with induction of ischemia/reperfusion.

Notes: *P < 0.05 vs control; ^&P < 0.05 vs model; ^#P < 0.05 vs PNS-NP; ^$P < 0.05 vs PNS-LP.

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1.

Figure 6 Effect of different PNS preparations on percent of infarction volume of rats with induction of ischemia/reperfusion.

Notes: *P < 0.05 vs control; ^&P < 0.05 vs model; ^#P < 0.05 vs PNS-NP; ^$P < 0.05 vs PNS-LP.

Abbreviations: PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; R1, notoginsenoside R1; Rb1, ginsenoside Rb1; Rg1, ginsenoside Rg1.

Table 3 Effect of different PNS preparations on the biochemical parameters (n = 10)

Groups	H2O2 (mmol/L)	SOD (U/mgprot)	MDA (nmol/mgprot)	LDH (U/L)
Control group	2.12 ± 0.82^&	30.3 ± 4.9^&	0.107 ± 0.11^&	3466.5 ± 155^&
Model group	5.45 ± 0.64*	11.4 ± 5.8*	0.210 ± 0.02*	6224.5 ± 210.7*
PNS solution	4.27 ± 1.05*	18.7 ± 3.2*,&	0.19 ± 0.02*	5224.7 ± 211.7*,&
PNS-NP	5.90 ± 1.08*,^#	32.1 ± 2.93*,&,#	0.18 ± 0.02*,&	5434.6 ± 216.4*,&,#
PNS-LP	4.96 ± 1.33*,^¥	22.7 ± 4.7*,&,#,¥	0.12 ± 0.03*,&,#,¥	4304.6 ± 143.0*,&,#,¥
PNS-HLV	3.12 ± 0.86*,&,#,¥,∃	38.0 ± 6.9*,&,#,¥,∃	0.14 ± 0.01*,&,#,¥,∃	4022.3 ± 187.3*,&,#,¥,∃

Notes:

* P < 0.05 vs Control group;

& P < 0.05 vs Model group;

# P < 0.05 vs PNS solution;

¥ P < 0.05 vs PNS-NP;

∃ P < 0.05 vs PNS-LP.

Abbreviations: LDH, lactate dehydrogenase; MDA, malondialdehyde; PNS, panax notoginsenoside; PNS-HLV, panax notoginsenoside-loaded core-shell hybrid liposomal vesicles; PNS-LP, PNS-loaded liposomes; PNS-NP, PNS-loaded nanoparticles; SOD, superoxide dismutase.