PLGA nanoparticles for the oral delivery of nuciferine: preparation, physicochemical characterization and in vitro/in vivo studies

Figures & data

Figure 1. (A) Encapsulation efficiency (EE%) and drug loading (DL%) of nanoparticles based on various amount of NUC adding (mean ± SD, n = 3). FTIR spectra (B) and DSC curves (C) of NUC, PLGA and NUC-PLGA-NPs. Size distribution (D) and zeta potential (E) of PLGA. Size distribution and a representative TEM image (F) and zeta potential (G) of NUC-PLGA-NPs. (H) In vitro release of NUC from NUC-PLGA-NPs in simulating gastric fluid at pH 1.2 and in simulating intestinal fluid at pH 6.8 over a period of one week (mean ± SD, n = 3).

Figure 2. Cellular uptake of free coumarin-6 (A) and coumarin-6-loaded NPs (B) against HepG2. Scale bar: 50 μm.

Figure 3. Cell viability (A) (mean ± SD, n = 3) and apoptosis (B) of HepG2 cells treated various formulations. (C) The effect of NUC on TG accumulated HepG2 of OA-induced hepatic steatosis. (D) Relative integrated option density (IOD) value was quantitated using Image Pro Plus 6.0 (mean ± SD, n = 3). *p < 0.05.

Figure 4. Mean plasma concentration–time curves of NUC (mean ± SD, n = 6).

Table 1. Pharmacokinetic parameters of NUC (mean ± SD, n = 6).

Administration	Units	n-NUC, IV	n-NUC, IG	NUC-PLGA-NPs, IG
Dose	mg/kg	0.2	5	5
t1/2	h	0.6 ± 0.2	0.8 ± 0.4	1.8 ± 0.2^a
Cmax	μg/mL	_	63.4 ± 19.0	77.9 ± 4.9
tmax	min	_	0.6 ± 0.2	1.3 ± 0.3^a
AUCt	min μg/mL	119 ± 34.1	118.2 ± 52.5	400.2 ± 64.4^b
Fabs	%	_	4.2 ± 1.3	13.5 ± 1.9^b
Frel	%	_	_	330 ± 61

t_1/2: half-life time; C_max: peak concentration; t_max: time to reach C_max; AUC_t: total area under curve; F_abs: absolute bioavailability; F_rel: relative bioavailability; NUC: nuciferine; IV: intravenous administration; IG: intragastric administration; NPs: nanoparticles

^a p < 0.05 and ^bp < 0.01 versus n-NUC

Table 2. Serum indexes for male Sprague Dawley rats after 2, 4, 6 and 8 weeks of treatment (mean ± SD, n = 6).

		Serum indexes (mmol/L)
Time	Group	TC	TG	HDL-C	LDL-C
2 weeks	NC	1.64 ± 0.13	0.44 ± 0.20	2.12 ± 0.22	0.36 ± 0.14
	HC	2.78 ± 0.18	0.42 ± 0.13	1.41 ± 0.23	0.51 ± 0.12
	n-NUC	2.56 ± 0.22	0.45 ± 0.13	1.99 ± 0.26^b	0.52 ± 0.25
	NUC-PLGA-NPs	2.33 ± 0.22^b	0.45 ± 0.11	2.00 ± 0.26^b	0.46 ± 0.27
4 weeks	NC	1.64 ± 0.23	0.38 ± 0.20	2.12 ± 0.27	0.40 ± 0.24
	HC	2.55 ± 0.13	0.51 ± 0.20	1.44 ± 0.17	0.52 ± 0.16
	n-NUC	2.50 ± 0.17	0.47 ± 0.15	1.99 ± 0.32^b	0.52 ± 0.09
	NUC-PLGA-NPs	2.2 ± 0.21^b,d	0.41 ± 0.19	2.03 ± 0.30^b	0.39 ± 0.15
6 weeks	NC	1.68 ± 0.29	0.40 ± 0.16	2.08 ± 0.16	0.40 ± 0.93
	HC	2.74 ± 0.19	0.48 ± 0.26	1.39 ± 0.13	0.45 ± 0.11
	n-NUC	2.40 ± 0.22^a	0.41 ± 0.18	1.63 ± 0.206^a	0.54 ± 0.08
	NUC-PLGA-NPs	2.11 ± 0.22^c,d	0.41 ± 0.20	2.06 ± 0.27^c,d	0.49 ± 0.20
8 weeks	NC	1.72 ± 0.30	0.40 ± 0.22	2.03 ± 0.28	0.39 ± 0.17
	HC	2.8 ± 0.18	0.54 ± 0.20	1.34 ± 0.26	0.48 ± 0.13
	n-NUC	1.93 ± 0.26^c	0.45 ± 0.18	1.76 ± 0.18^b	0.47 ± 0.20
	NUC-PLGA-NPs	1.38 ± 0.15^c,f	0.30 ± 0.13^d	2.17 ± 0.24^c,e	0.31 ± 0.11^d

NC: normal control; HC: hyperlipidemia control; NUC: nuciferine; NPs: nanoparticles; TC: total cholesterol; TG: triglycerides; HDL-C: high density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol

^a p < 0.05, ^bp < 0.01 and ^cp < 0.001 versus HC in various weeks, respectively.

^d p < 0.05, ^ep < 0.01 and ^fp < 0.001 versus n-NUC in various weeks, respectively.