Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

Figures & data

Table 1 Physicochemical properties of ZnO and ZLH-nanohybrid, EAN

Compounds	C (%)	H (%)	Zn (%w/w)	a Anion (%w/w)	BET surface area (m^2/g)	BJH pore diameter (Å)	BJH pore volume (cm^3/g)
ZnO	–	–	(80.3)	–	6.4	111	0.010
EAN	32.7	2.6	29.3	58.8	3.6	170	0.007

a Notes: Estimated from CHNS analysis; value in the parentheses is the theoretical value.

Abbreviations: BJH, Barret–Joyner–Helenda; BET, Brunauer, Emmett and Teller; C, carbon; H, hydrogen; EAN, ellagic acid nanohybrid; ZnO, zinc oxide; ZLH, zinc layered hydroxide.

Table 2 Correlation coefficient, rate constant, and half time obtained by fitting the data of the release of EA from EAN into 0.1 M Na₂CO₃ and 0.1 M Na₃PO₄; the equation of kinetic models used for the fitting is also indicated

Aqueous solution	Saturated release %	r^2				Rate constant (k) pseudo-second order (g/mg·h)	t1/2 pseudo-second order (h)
		Zeroth-order	First-order	Pseudo-second order	Parabolic diffusion
Na2CO3	69%	0.6683	0.7635	0.9985	0.7997	0.0044	3.03
Na3PO4	94%	0.3963	0.7381	0.9996	0.5926	0.0175	0.61
Kinetic equation	Zeroth-order ${\text{M}}_{\text{t}}-{\text{M}}_{\text{o}}=-{\text{k}}_{\text{o}}\text{t}$	First-order $\text{log}({\text{M}}_{\text{t}}/{\text{M}}_{\text{o}})=-{\text{k}}_1\text{t}$		Pseudo-second order ${\text{t}/\text{q}}_{\text{t}}=1/\text{h}+\text{t}/{\text{q}}_{\text{e}}$		Parabolic diffusion $(1-{\text{M}}_{\text{t}}/{\text{M}}_{\text{o}})/\text{t}={\text{K}}_{\text{d}}{\text{t}}^{-0.5}+\text{a}$

Notes: M_o is the EA content remained in the ZLH at release time o, M_t is the EA content remained in the ZLH at release time t, q_e is the equilibrium release amount and q_t is the release amount at time t, h = k₂q_e ², k the corresponding release rate constant, a is constant whose chemical significance is not clearly resolved.⁴³

Abbreviations: EA, ellagic acid; ZLH, zinc layered hydroxide.

Figure 1 PXRD patterns of ZnO (A), EAN (B) and EA (C).

Abbreviations: PXRD, powder X-ray diffraction; EA, ellagic acid; EAN, ellagic acid nanohybrid.

Figure 2 Molecular structure of EA and three-dimensional molecular size of EA (A) and spatial orientation of EA in ZLH inorganic interlayers (B).

Abbreviations: EA, ellagic acid; ZLH, zinc layered hydroxide.

Figure 3 FTIR spectrum of EA (A) and EAN (B).

Abbreviations: FTIR, Fourier transform infra-red; EA, ellagic acid; EAN, ellagic acid nanohybrid.

Figure 4 TGA-DTG thermogravimetric analysis of EA (A) and EAN (B).

Abbreviations: TGA–DTG, thermogravimetric and differential thermogravimetric analyses; EA, ellagic acid; EAN, ellagic acid nanohybrid.

Figure 5 Adsorption–desorption isotherms (A) and BJH pore size distribution (B) for ZnO and EAN.

Abbreviations: BJH, Barret–Joyner–Halenda; EAN, ellagic acid nanohybrid.

Figure 6 FESEM image of ZnO (A) and EAN (B) and EAN at higher magnification (C).

Abbreviations: FESEM, field emission scanning electron microscope; EA, ellagic acid; EAN, ellagic acid nanohybrid.

Figure 7 Solid-state UV-Vis spectra of pure EA and its nanohybrid, EAN (A) and their Kubelka-Munk plot of EA, EAN and ZnO (B).

Abbreviations: EA, ellagic acid; EAN, ellagic acid nanohybrid.

Figure 8 Release profiles of EA from the EAN in the aqueous solution containing 0.1 M Na₂CO₃ (A) and 0.1 M Na₃PO₄ (B). Inset shows release of free EA into Na₂CO₃ (C) and Na₃PO₄ (D).

Abbreviations: EA, ellagic acid; EAN, ellagic acid nanohybrid.

Figure 9 Fitting of the data of EA released from the EAN into solution to the zeroth-, first-, pseudo-second-order kinetics, and parabolic diffusion for 0.1 M Na₂CO₃ (A, B, C, and D respectively) and Na₃PO₄ (E, F, G, and H, respectively).

Abbreviations: EA, ellagic acid; EAN, ellagic acid nanohybrid; ZnO, zinc oxide.

Table 3 Viability of hepatocytes during incubation with EA and EAN

	0 h	0.5 h	1.0 h	3.0 h	6.0 h
Control (1% DMSO)	97.4 ± 1.0^aw	96.8 ± 0.8^aw	96.2 ± 1.4^aw	94.3 ± 1.2^aw	92.5 ± 1.6^ax
25 μg/mL EA	98.2 ± 1.0^aw	94.3 ± 1.3^ax	92.5 ± 1.2^bx	89.4 ± 2.4^by	83.4 ± 2.5^by
25 μg/mL EAN	97.3 ± 1.1^aw	94.8 ± 0.8^ax	90.5 ± 1.8^by	85.3 ± 4.3^bz	77.2 ± 5.7^cz
25 μg/mL ZnO	96.7 ± 1.5^aw	93.2 ± 1.0^bx	88.5 ± 1.3^cy	84.3 ± 5.7^by	73.4 ± 6.2^cz

Notes: N = 3. Values are mean ± SD. Means with different superscript (a–c) differs significantly (P < 0.05) by ANOVA and Duncan multiple post-test in the same column and (w–z) differs significantly in the same row.

Abbreviations: EA, ellagic acid; EAN, ellagic acid nanohybrid; ZnO, zinc oxide.

Figure 10 The effect of EA, EAN, and ZnO on the viability of rat hepatocyte cells at the concentration of 25 μg/mL.

Abbreviations: EA, ellagic acid; EAN, ellagic acid nanohybrid; ZnO, zinc oxide.

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