Experimental Design Modelling and Optimization of the Intercalation of Levofloxacin and Salicylic Acid into the Structure of ZnAl-LDH by Response Surface Method: <i>in vitro</i> Study of Release Kinetics, Antibacterial and Anti-Inflammatory Activities

Vy, Ngo T. T.; Khanh, Dang N. N.; Khoa, Le H.; Phat, Nguyen T.; Thang, Nguyen Q.; Trung, Le H.; Nhu, Nguyen T. H.; Phuong, Doan T. M.; Phuong, Nguyen T. K.

doi:10.21577/0103-5053.20230180

Acessibilidade / Reportar erro

Brasil

Journal of the Brazilian Chemical Society

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Article • J. Braz. Chem. Soc. 35 (5) • 2024 • https://doi.org/10.21577/0103-5053.20230180 copy

Experimental Design Modelling and Optimization of the Intercalation of Levofloxacin and Salicylic Acid into the Structure of ZnAl-LDH by Response Surface Method: in vitro Study of Release Kinetics, Antibacterial and Anti-Inflammatory Activities

Authorship SCIMAGO INSTITUTIONS RANKINGS

In recent years, solid-state engineering has emerged as a promising method for improving the stability and potency of antibiotics and anti-inflammatory drugs. This study focuses on the design and optimization of the intercalation of levofloxacin (an antibiotic drug) and salicylic acid (an anti-inflammatory drug) into zinc-aluminium-layered double hydroxide galleries using response surface method. Release studies revealed that a burst release phenomenon was observed at the beginning of the release assay, and the pH value (in the range of 5.8-7.4) had very little influence on the levofloxacin and salicylic acid release efficiency. This indicates that zinc-aluminium-layered double hydroxide could be an effective inorganic carrier for levofloxacin and salicylic acid over a wide range of pH values. Four kinetic models were used to study the release kinetics and the drug release mechanism was also discussed. In addition, the intercalation of levofloxacin and salicylic acid into zinc-aluminium-layered double hydroxide exhibited enhanced antibacterial activity against Gram-positive Bacillus subtilis. The cell viability assay revealed non-toxic behavior of levofloxacin and salicylic acid intercalated into zinc-aluminium-layered double hydroxide against the monocyte/macrophage-like cell line.

Keywords:
experimental design; optimization; response surface methodology; zinc-aluminium-layered double hydroxide; levofloxacin; salicylic acid

Coded values	Variable and range
Coded values	Temperature (X₁) / °C	time (X₂) / h	Amount of drug (X₃) / g
High (+1)	75.0	19.0	1.00
Medium (0)	65.0	17.5	0.75
Low (-1)	55.0	16.0	0.50

No.	Variable levels			LEV-LDH			SAL-LDH
	Temp. (X₁)	time (X₂)	Amount of drug (X₃)	Observed		Predicted LEV intercalated / %	Observed		Predicted SAL intercalated / %
	Temp. (X₁)	time (X₂)	Amount of drug (X₃)	TOC / mg	LEV intercalated / %	Predicted LEV intercalated / %	TOC / mg	SAL intercalated / %	Predicted SAL intercalated / %
1	-1	-1	-1	0.145	24.22	24.23	0.218	35.82	36.51
2	1	-1	-1	0.165	27.50	27.10	0.245	40.23	40.36
3	-1	1	-1	0.172	28.80	28.23	0.247	40.57	40.40
4	1	1	-1	0.175	29.24	29.56	0.260	42.74	42.74
5	-1	-1	1	0.158	26.40	26.04	0.236	38.76	38.82
6	1	-1	1	0.199	33.19	33.72	0.279	45.86	46.09
7	-1	1	1	0.172	28.80	29.16	0.254	41.77	41.70
8	1	1	1	0.211	35.35	35.31	0.293	48.08	47.45
9	-1	0	0	0.173	28.92	29.48	0.257	42.22	41.71
10	1	0	0	0.206	34.40	33.99	0.281	46.24	46.51
11	0	-1	0	0.191	31.88	32.09	0.279	45.79	44.69
12	0	1	0	0.209	34.96	34.89	0.283	46.45	47.32
13	0	0	-1	0.185	31.00	31.63	0.276	45.38	44.73
14	0	0	1	0.215	35.90	35.41	0.291	47.83	48.24
15	0	0	0	0.210	35.10	34.79	0.286	47.03	47.42
16	0	0	0	0.209	34.95	34.79	0.286	46.94	47.42
17	0	0	0	0.207	34.60	34.79	0.291	47.82	47.42

Source of variation	LEV intercalated				SAL intercalated
Source of variation	Mean squares	Degrees of freedom	F-value	p-value	Mean squares	Degrees of freedom	F-value	p-value
Regression	23.46	9	66.58	< 0.0001	23.21	9	36.84	< 0.0001
X₁	50.78	1	114.12	< 0.0001	57.65	1	91.51	< 0.0001
X₂	19.50	1	55.35	0.0001	17.29	1	27.45	0.0012
X₃	35.65	1	101.17	< 0.0001	30.84	1	48.95	0.0002
X₁²2 Ladewig, K.; Niebert, M.; Xu, Z. P.; Gray, P. P.; Lu, G. Q. M.; Biomaterials 2010, 31, 1821. [Crossref] Crossref...	25.02	1	70.99	< 0.0001	29.34	1	46.57	0.0002
X₂²2 Ladewig, K.; Niebert, M.; Xu, Z. P.; Gray, P. P.; Lu, G. Q. M.; Biomaterials 2010, 31, 1821. [Crossref] Crossref...	5.40	1	12.78	0.0090	5.40	1	8.57	0.0221
X₃²2 Ladewig, K.; Niebert, M.; Xu, Z. P.; Gray, P. P.; Lu, G. Q. M.; Biomaterials 2010, 31, 1821. [Crossref] Crossref...	4.29	1	12.18	0.0101	2.34	1	3.71	0.0954
X₁X₂	1.19	1	3.37	0.1091	1.15	1	1.82	0.2191
X₁X₃	11.57	1	32.83	0.0007	5.83	1	9.26	0.0188
X₂X₃	0.39	1	1.10	0.3295	0.52	1	0.82	0.3959
Residual	0.35	7	-	-	0.63	7	-	-
Lack of fit	0.4670	5	7.09	0.1282	0.7882	5	3.36	0.2450
Pure error	0.0658	2	-	-	0.2344	2	-	-
Total corrected	13.35	16	-	-	13.33	16	-	-
	RSD = 0.5936 R² = 0.9885		Predicted R² = 0.8496 Adjusted R² = 0.9736		RSD = 0.7937 R² = 0.9793		Predicted R² = 0.8302 Adjusted R² = 0.9527

Drug	Predicted value / %	Observed value / %	Relative error / %
LEV	36.56	35.35	3.34
SAL	49.18	48.00	2.40

Sample	Element^a a Observed data (the data are computed from the proposed empirical formulas) using ICP-OES (PerkinElmer, USA) to analyze Zn and Al; ion chromatography (IC) (Metrohm, Switzerland) to analyze F and CHNSO elemental analysis (Mettler Toledo, USA) to analyze C, H, O and N. LEV-LDH: levofloxacin intercalated into layered double hydroxide; SAL-LDH: salicylic acid intercalated into layered double hydroxide. / %
Sample	Zinc (Zn)	Aluminium (Al)	Oxygen (O)	Organic carbon (C)	Nitrogen (N)	Hydrogen (H)	Fluor (F)
LEV-LDH	34.76 (34.76)	4.24 (4.24)	30.83 (29.95)	21.15 (21.15)	4.11 (4.20)	3.45 (3.44)	1.86 (1.86)
SAL-LDH	31.48 (31.48)	3.92 (3.92)	32.32 (33.40)	29.21 (29.21)	-	3.10 (3.13)	-

Sociedade Brasileira de Química Instituto de Química - UNICAMP, Caixa Postal 6154, 13083-970 Campinas SP - Brazil, Tel./FAX.: +55 19 3521-3151 - São Paulo - SP - Brazil
E-mail: office@jbcs.sbq.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] *e-mail: nguyenthikimp@yahoo.ca