Improved uptake and therapeutic intervention of curcumin via designing binary lipid nanoparticulate formulation for oral delivery in inflammatory bowel disorder

Figures & data

Table 1. Various batches of C-SBLNs prepared by varying processing variables.

Formulation code	Lipid		Sonica-tion time (min)	Surfactant		Particle size (nm ± SD)		Zeta potential (mV ± SD)	Polydispersity index (PDI ± SD)	Entrapment efficiency (%±SD)
	Stearic acid (mg)	Tristearin (mg)		PF-68 (% w/v)	Tween-80 (% w/v)
						Before Lyophilization	After Lyophilization
S1	200	–	7.5	0.50	–	530.14 ± 21.36	554.80 ± 34.52	−18.21 ± 3.14	0.41 ± 0.02	67.89 ± 6.28
S2	150	50	7.5	0.50	–	135.24 ± 24.65	161.47 ± 31.56	−19.87 ± 2.98	0.35 ± 0.01	71.47 ± 5.46
S3	133.33	66.67	7.5	0.50	–	169.56 ± 25.13	189.25 ± 29.41	−23.45 ± 3.45	0.30 ± 0.02	78.23 ± 7.44
S4	100	100	7.5	0.50	–	193.23 ± 29.36	210.56 ± 41.22	−28.01 ± 4.14	0.19 ± 0.03	83.12 ± 6.57
S5	66.67	133.33	7.5	0.50	–	245.23 ± 25.14	271.86 ± 29.68	−28.19 ± 4.75	0.26 ± 0.03	81.04 ± 5.14
S6	100	100	7.5	0.25	–	408.65 ± 34.25	444.62 ± 31.02	−24.14 ± 5.05	0.43 ± 0.02	72.08 ± 4.78
S7	100	100	7.5	0.75	–	167.81 ± 30.13	181.23 ± 36.54	−26.04 ± 4.75	0.20 ± 0.04	75.41 ± 6.32
S8	100	100	7.5	–	0.50	444.12 ± 32.01	456.01 ± 29.23	−22.17 ± 3.19	0.36 ± 0.03	74.14 ± 5.38
S9	100	100	5.0	0.50	–	490.01 ± 29.35	501.45 ± 31.78	−20.18 ± 4.84	0.42 ± 0.02	73.12 ± 6.12
S10	100	100	10.0	0.50	–	120.36 ± 25.98	138.56 ± 24.87	−23.56 ± 5.46	0.25 ± 0.03	75.06 ± 7.22

Figure 1 (A) ATR-FTIR spectra of curcumin, stearic acid, tristearin, lecithin, physical mixture and optimized C-SBLNs formulation, respectively. (B) Thermograms of curcumin, stearic acid, tristearin, lecithin, physical mixture and optimized C-SBLNs formulation, respectively. (C) Powder X-ray diffractograms of curcumin, stearic acid, tristearin, lecithin, physical mixture and optimized C-SBLNs formulation, respectively. (D) Scanning electron microscopy of optimized C-SBLNs formulation.

Figure 2 Dissolution profile of optimized C-SBLNs in pH progressive media.

Table 2. Physical stability of C-SBLNs incubated in simulated gastrointestinal fluids.

Parameter	Water		HCl Buffer pH 1.2		Phosphate buffer pH 6.8		Phosphate buffer pH 7.4
Incubation time (h)	0	2	0	2	0	2	0	2
Size (nm ± SD)	292.35 ± 23.13	293.14 ± 24.68	689.23 ± 45.23	Aggregate (395.6 ± 56.14 µm)	298.23 ± 34.12	286.41 ± 31.68	300.12 ± 28.12	276.32 ± 26.17
Zeta potential (mV ± SD)	−28.36 ± 4.25	−27.69 ± 4.56	−10.68 ± 0.98	−4.12 ± 0.87	−24.53 ± 5.78	−25.89 ± 6.12	−23.08 ± 7.09	−22.36 ± 5.46
Polydisper-sity index (PDI ± SD)	0.215 ± 0.02	0.216 ± 0.01	0.645 ± 0.03	0.956 ± 0.03	0.224 ± 0.01	0.199 ± 0.02	0.229 ± 0.01	0.236 ± 0.02

Table 3. Effect of storage conditions on the stability of optimized C-SBLNs formulation.

Duration (month)	Storage condition	Particle size (nm ± SD)	Zeta potential (mV ± SD)	Polydispersity index (PDI ± SD)	Entrapment efficiency (%±SD)	Cumulative percentage release (%±SD)
0	–	210.56 ± 41.22	−28.01 ± 4.14	0.191 ± 0.03	83.12 ± 6.57	97.98 ± 5.23
1	4 ± 2 ºC/ 65 ± 5% RH	214.41 ± 30.12	−27.32 ± 4.38	0.181 ± 0.04	82.23 ± 4.13	96.04 ± 7.89
	25 ± 2 °C/ 60 ± 5% RH	226.21 ± 36.08	−26.48 ± 6.14	0.198 ± 0.05	81.31 ± 4.44	94.87 ± 6.71
3	4 ± 2 ºC/ 65 ± 5% RH	219.03 ± 31.2	−28.11 ± 3.69	0.203 ± 0.03	81.87 ± 4.87	95.68 ± 6.19
	25 ± 2 °C/ 60 ± 5% RH	296.25 ± 40.17	−24.14 ± 4.56	0.302 ± 0.04	79.23 ± 3.04	93.05 ± 4.52

Figure 3 Amount of curcumin in stomach, small intestine and colon after oral administration of curcumin dispersion and optimized C-SBLNs to guinea pigs suffering from colitis, respectively.

Figure 4 Effect of curcumin dispersion and optimized C-SBLNs formulation on (A) inflammatory biomarkers (MPO and TNFα) (B) oxidative stress biomarkers (LPO and protein carbonyl content) and (C) histopathological evaluation of colon of (a) PBS-treated, (b) PBS-DSS treated, (c) curcumin-DSS treated and (d) C-SBLNs-DSS treated guinea pig, respectively. The values of biomarkers of DSS-treated group were considered to be 100 %. Optimized formulation showed statistically significant reduction in per cent level of biomarkers as well as histopathological changes with respect to DSS-treated control (p<.001) as well as curcumin (p<.05).