Characterization of the host–guest complex of a curcumin analog with β-cyclodextrin and β-cyclodextrin–gemini surfactant and evaluation of its anticancer activity

Figures & data

Figure 1 Chemical structures of (A) CD, (B) NC 2067, (C) CDgemini surfactant (ester linker), and (D) CDgemini surfactant (amide linker).

Abbreviations: CD, β-cyclodextrin; CDgemini surfactant, β-cyclodextrin-gemini surfactant.

Figure 2 Diffractograms of (A) CD (a), NC 2067 (b), physical mixture (c), and inclusion complex of NC 2067 and CD (d); and (B) CDgemini surfactant (a), NC 2067 (b), physical mixture (c), and inclusion complex of NC 2067 and CDgemini surfactant (d).

Abbreviations: au, arbitrary units; CD, β-cyclodextrin; CDgemini surfactant, β-cyclodextrin-gemini surfactant.

Figure 3 FTIR spectra of (A) CD (a), NC 2067 (b), physical mixture (c), and inclusion complex of NC 2067 and CD (d); and (B) CDgemini surfactant (a), NC 2067 (b), physical mixture (c), and inclusion complex of NC 2067 and CDgemini surfactant (d).

Note: Expansions for the 1,720–1,380 cm⁻¹ region are illustrated in the insets.

Abbreviations: au, arbitrary units; CD, β-cyclodextrin; CDgemini surfactant, β-cyclodextrin-gemini surfactant; FTIR, Fourier-transform infrared.

Figure 4 TGA thermograms of (A) CD, NC 2067, physical mixture, and inclusion complex of NC 2067 and CD; and (B) CDgemini surfactant, NC 2067, physical mixture, and inclusion complex of NC 2067 and CDgemini surfactant.

Abbreviations: CD, β-cyclodextrin; CDgemini surfactant, β-cyclodextrin-gemini surfactant; TGA, thermogravimetric analysis.

Table 1 Size of different nanoparticulate formulations and corresponding PDI

NC 2067/CDgemini surfactant nanoparticles	NC 2067-to-CDgemini surfactant mole ratio	Size (nm) ± SD	PDI
Ester linker	1:0.5	160±3	0.1
	1:1	140±1	0.2
	1:2	101±2	0.3
Amide linker	1:0.5	199±6	0.3
	1:1	131±3	0.2
	1:2	131±1	0.2

Note: Sizes are the average of three to five measurements ± SD.

Abbreviations: CD, β-cyclodextrin; CDgemini surfactant, β-cyclodextrin-gemini surfactant; PDI, polydispersity index; SD, standard deviation.

Figure 5 SAXS/WAXS patterns of (A) CDgemini surfactant; and complexes of NC 2067 with CDgemini surfactant at three different mole ratios of (B) 1:2, (C) 1:1, and (D) 1:0.5. Arrows show the peaks corresponding to precipitated NC 2067.

Abbreviations: CD, β-cyclodextrin; CDgemini surfactant, β-cyclodextrin-gemini surfactant; SAXS/WAXS, small- and wide-angle X-ray scattering.

Table 2 IC₅₀ values of melphalan in acidified ethanol and NC 2067 in DMSO and various CDgemini surfactant formulations and percentage intrinsic toxicity of the CDgemini surfactants

Anticancer agent	Delivery agent/solvent	Mole ratio of drug to delivery agent	IC50 (μM) ± SD	% toxicity of CDgemini surfactant (200 μM) ± SD
Melphalan	Acidified ethanol	NA	40±9	NA
NC 2067	DMSO	NA	0.5±0.1	NA
	CDgemini surfactant (amide linker)	1:2	2.1±0.3	94.6±0.5
	CDgemini surfactant (ester linker)	1:0.5	2.2±0.2	18±6
		1:1	2.4±0.4
		1:2	2.0±0.25

Abbreviations: CDgemini surfactant, β-cyclodextrin-gemini surfactant; DMSO, dimethyl sulfoxide; IC₅₀, half-maximal inhibitory concentration; SD, standard deviation; NA, not applicable.

Table S1 Most intense peaks in diffractograms of CD, NC 2067, physical mixture, and their inclusion complex powder samples (20 peaks have been shown)

	CD		NC 2067		Physical mixture		Inclusion complex
	2θ (°)	d (Å)	2θ (°)	d (Å)	2θ (°)	d (Å)	2θ (°)	d (Å)
1	8.35	7.10	3.89	15.22	3.93	15.07	1.95	30.36
2	7.01	8.45	4.07	14.55	13.89	4.27	13.95	4.25
3	12.95	4.58	13.91	4.27	13.17	4.50	14.41	4.12
4	11.29	5.25	12.87	4.61	11.85	5.00	13.33	4.45
5	13.81	4.30	13.03	4.55	12.79	4.64	15.87	3.74
6	12.51	4.74	13.25	4.48	8.39	7.06	14.83	4.00
7	11.77	5.04	13.41	4.42	12.51	4.74	12.47	4.76
8	11.61	5.11	12.67	4.68	11.49	5.16	12.27	4.83
9	15.07	3.94	16.13	3.68	7.19	8.24	11.75	5.05
10	10.15	5.84	10.57	5.61	16.07	3.70	11.45	5.18
11	14.23	4.17	1.51	39.21	10.51	5.64	16.53	3.59
12	17.89	3.32	11.91	4.98	15.75	3.77	8.35	7.10
13	2.91	20.34	18.91	3.14	16.89	3.52	20.47	2.91
14	16.61	3.58	15.95	3.72	9.89	5.99	10.25	5.78
15	9.71	6.10	20.09	2.96	15.31	3.88	9.33	6.35
16	16.11	3.69	17.03	3.49	13.65	4.35	18.81	3.16
17	7.63	7.76	11.55	5.13	18.81	3.16	7.07	8.38
18	7.81	7.59	15.01	3.96	13.47	4.40	19.39	3.07
19	17.53	3.39	5.19	11.41	18.03	3.30	21.59	2.76
20	5.97	9.92	9.89	5.99	14.33	4.14	18.37	3.24

Abbreviation: CD, β-cyclodextrin.