Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate–zinc aluminum-layered double-hydroxide nanocomposites

Figures & data

Figure 1 X-ray diffraction patterns of PASA-D (A), PASA-I (B) and free PASA (C).

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method.

Figure 2 Three-dimensional structure of PASA (A) and molecular structural models of PASA intercalated between interlayers of Zn/Al-LDH (B).

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method; Zn/Al-LDH, zinc/aluminum-layered double hydroxide.

Figure 3 Fourier-transform infrared spectra of (A) PASA, (B) PASA-D, and (C) PASA-I.

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method.

Table 1 Assignments of FTIR absorption bands of free PASA, PASA-D and PASA-I nanocomposites

Assignments	Free PASA	PASA-D	PASA-I
ν (O–H) and ν (N–H)	3,490, 3,381	3,343 in the layer; H2O	3,340
ν (COOH)	1,609	–	–
ν (C–C)	1,519, 1,437	1,507, 1,451	1,505, 1,446
δ (O–H) in plane	1,283, 1,163	1,294, 1,157	1,292, 1,156
δ (C–H) in plane	1,109	1,090	1,090
Ring-breathing mode	962	972	1,012
νas (COO^−)	–	1,564	1,560
νs (COO^−)	–	1,361	1,355

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method; FTIR, fourier transform infrared spectroscopy.

Table 2 Chemical compositions of PASA, PASA-D, and PASA-I nanocomposites

Samples	Zn%a	Al%a	C%b	N%b	C/N	Drug%	Zn^2+/Al^3+	X
PASA	–	–	51.7	8.3	6.2	–	–	–
PASA-D	37.9	4.2	19.4	2.1	9.2	22.8c	3.8	0.21
PASA-I	37.9	3.8	16.9	1.5	11.3	16.6c	4.1	0.19

Notes:

a Calculated from ICP data

b calculated from CHNS data

c calculated from UV data.

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method; UV, ultraviolet; CHNS, carbon, hydrogen, nitrogen, and sulfur; ICP, inductively coupled plasma; X, aluminium mole fraction.

Figure 4 Thermogravimetric analysis–differential thermogravimetric thermograms of PASA (A), PASA-D (B), and PASA-I (C).

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method.

Figure 5 Field-emission scanning electron micrographs of PASA-D (A and B) and PASA-I (C and D) nanocomposites at 50,000× and 100,000× magnifications.

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method.

Figure 6 Release profiles of PASA from PASA-D (A) and PASA-I (B) nanocomposites into PBS at pH 7.4 and 4.8. Insets show the release profiles of PASA from nanocomposite at initial 500 minutes time.

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method.

Table 3 Correlation coefficient (R ²), and rate constants (k) obtained by fitting the data of PASA release from PASA-D and PASA-I nanocomposites into PBS solution at pH 4.8 and 7.4

Samples	pH	Saturation release (%)	R ^2			Pseudo-second-order
			Pseudo-first-order	Pseudo-second-order	Parabolic diffusion model	Rate constant k (mg/min)
PASA-D	7.4	88	0.8298	0.9946	0.8842	1.5 × 10^−5
PASA-D	4.8	100	0.9129	0.9978	0.8369	3.3 × 10^−5
PASA-I	7.4	57	0.9692	0.9952	0.9580	1.7 × 10^−5
PASA-I	4.8	93	0.9103	0.9991	0.7849	5.2 × 10^−5

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method; PBS, phosphate-buffered saline.

Figure 7 (A–D) Data fit of PASA release from PASA-D and PASA-I nanocomposites into pseudo-second-order kinetic model at pH 7.4 and 4.8.

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA nanocomposite prepared by direct method; PASA-I, PASA nanocomposite prepared by indirect method.

Figure 8 Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay) of 3T3 mouse fibroblast cells and human lung fibroblast MRC-5 cells exposed to various gradient concentrations at 24, 48, and 72 hours’ exposure time. The data presented are means ± standard deviation of triplicate samples.

Abbreviations: PASA, para-amino salicylic acid; PASA-D, PASA by direct method; PASA-I, PASA by indirect method; ZLDH, zinc/aluminum-layered double hydroxide.