Solubilisation and Enhanced Oral Absorption of Curcumin Using a Natural Non-Nutritive Sweetener Mogroside V

Figures & data

Table 1 Solubilisation of CUR Using Different Formulations

Preparation	Formulation	Fold Change Solubility	Fold Change Bioavailability	Ref.
Solid dispersions	CUR: Mog-V=1:10	6712	29	-
	CUR: HPMC=1:1	-	17	[8]
	CUR:TPGS: mannitol= 1:10:15	-	65	[36]
Cyclodextrins	β-CD	2.3	-	[9]
Microemulsions	Kolliphor RH40	-	4.0	[37]
Nanoparticles	TPGS, Brij78	-	12.3	[38]
Liposomes	TMC	-	1.6	[39]
	Carbopol	-	2.2	[40]
Micelles	Pluronic	-	-	[12]

Abbreviations: HPMC, Hydroxypropyl Methylcellulose; β-CD, β-Cyclodextrin; TPGS, D-Alpha-Tocopheryl Poly (Ethylene Glycol) Succinate 1000; Brij78, Alkyl-PEO; TMC, N-Trimethyl Chitosan Chloride.

Table 2 Studies Using Glycosides to Solubilise Poorly Water-Soluble Drugs

Glycoside	Molecular Weight	CMC (mg/mL)	Active Ingredients to Glycoside Ratio (w/w)	Micelle Size (nm)	Solubility (mg/mL)	Enhancement Ratio of Solubility^a	Enhancement Ratio of AUC^a	Reference
Hesperidin-G	772.7	5.0	Naringenin: Hesperidin-G =1:20	-	3.5± 0.2	77	-	[41]
			Flurbiprofen: Hesperidin-G =1:10	-	0.5	10	2.8	[42]
			Probucol: Hesperidin-G =1:10	-	0.005	1000	5.3	[43]
			Glibenclamide: Hesperidin-G =1: 5	-	-	-	6	[44]
			Naringenin: Hesperidin-G =1:10	-	1.4	30	-	[16]
Rutin-G	759	5.0	Tranilast: Rutin-G=1:10	2.9	0.04	32.2	36.4	[45]
			Ipriflavone: Rutin-G=1:10	-	0.003	3	4.3	[46]
			Folic acid: Rutin-G= 1:2	<100	1	100	-	[47]
			Flurbiprofen: Rutin-G =1:10	-	-	-	2.2	[17]
Stevia-G	965.0	12	Propolis: Stevia-G =1:10	350	-	-	6.4	[48]
			Curcumin: Stevia-G=1:10	-	0.5	1600	-	[29]
			Curcumin: Stevia-G: PVP K-30=1:10:0.5	-	4.1	13,000	6.7	[29]
			Indomethacin: Stevia-G=1:10	-	0.04	5	-	[49]
			Flurbiprofen: Stevia-G=1:10	-	0.06	1.6	2.2	[43]
			Probucol: Stevia-G=1:10	-	0.007	1340	9.8	[43]
			Mefenamic acid: Stevia-G: LTAC=1:10:1	-	-	-	-	[50]
			Naringenin: Stevia-G=1:10	3	1.8	36	-	[18]
			Quercetin: Stevia-G: PVP =1:10:5	-	0.1	5	-	[51]
Stevioside	804.9	4.9	-	4.7	1.0	45	-	[52]
Rebaudioside A	967.0	-	Naringenin: Rebaudioside A=1:24	5.2	24.6	2198	2.1	[53]
Mogroside V	1287.4	5.5	Silybin: Mog-V =1:20	206	2.2	1931	24.5	[19]
			Curcumin: Mog-V=1:10	154	1.4	5712	29	-
ssβ-glucan	-	-	Quercetin: ssβ-glucan=1:10	-	-	-	-	[54]
Naringin-G	742.5	-	Pranlukast hemihydrate: Naringin-G =1:5	2.7	-	-	2.2	[55]
Rubusoside	642.7	-	Curcumin: Rubusoside=1:20	8	2.3	2318	-	[20]

Note: ^aAfter Solubilisation /Untreated Drug.

Abbreviations: PVP, Polyvinylpyrrolidone; Hesperidin-G, α-Glucosyl Hesperidin; Rutin-G, α-Glycosyl Rutin; Stevia-G, α-Glucosyl Stevia; Naringin-G, α-Glycosylated Naringin; LTAC, Lauryl Trimethyl Ammonium Chloride.

Figure 1 Chemical structures of (A) Mogroside V (Mog-V) and (B) Curcumin (CUR) with protons of representative chemical shifts numbered. Schematic representation of the solubilisation mechanism: self-assembly of Mog-V micelles in aqueous solution to encapsulate CUR (C).

Figure 2 Power X-ray diffraction diagrams and differential scanning calorimetry thermograms of (A) SDPs, (B) PMs, (C) Mog-V, and (D) CUR.

Figure 3 Particle size distribution of (A) Mog-V and (B) CUR/Mog-V SDPs in water (including the cumulative distribution curves of particle size). Dissolution profile of CUR in (C) pH 1.2, (D) pH 6.8 buffer solutions each containing 0.2% Tween 80 at 37°C. ■, CUR, ●, CUR/Mog-V SDPs.

Figure 4 ¹H NMR spectra of Mog-V solution at concentrations of 1–50 mg/mL recorded in D₂O (A). Plots of (B) δ_obs against 1/C and (C) log (C(δ_obs-δ_mon)) against log (C(δ_mic-δ_obs)) for the H-30 peak from the ¹H NMR spectra. 2D ¹H-¹H NOESY spectra of Mog-V at (D) 1 mg/mL (below CMC) and (E) 50 mg/mL (above CMC).

Figure 5 ¹H NMR spectra of (A) Mog-V, 50 mg/mL; (B) CUR/Mog-V SDPs, 55 mg/mL. 2D ¹H-¹H NOESY spectra of (C) Mog-V and (D) CUR/Mog-V SDPs.

Table 3 The Oral Absorption of CUR Crystal and CUR/Mog-V SDPs in Rats

Group	Cmax (ng/mL)	Tmax (min)	AUC0–t (μg·min/L)
CUR/Mog-V SDPs	663.1±331	15±0	45,665±14,926
CUR crystal	5.992±3.6	10±5.8	1577±491

Note: Data represent the rean ± SD of 4 rats.

Abbreviations: C_max, Maximum CUR concentration in plasma; T_max, Time to maximum concentration; AUC_0–T, Area under the curve.

Figure 6 Plasma concentration-time profiles in rats after oral administration of CUR crystal and CUR/Mog-V SDPs. ■, CUR; ●, CUR/Mog-V SDPs. N = 4.

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