Abstract
Hippuric acid (HA) was intercalated into a zinc-layered hydroxide (ZLH) by direct reaction of an aqueous suspension of zinc oxide with an aqueous solution of hippuric acid to obtain hippurate nanocomposite (HAN). Various concentrations of hippuric acid (0.05, 0.2, and 0.4 molar) were used for the synthesis of the nanocomposite. The as-synthesized HAN using 0.2 molar was found to give a well-ordered layered nanocomposite material with an increase in the basal spacing to 21.3 Å which indicated the insertion of hippurate organic moiety into the ZLH interlayers. The cytotoxicity of HAN in combination with cytarabine against human promyelocytic leukemia cells (HL-60) was tested using MTT cell viability assay and trypan blue dye exclusion assay. The combination of cytarabine with HAN showed higher tumor suppression efficiency as compared to that of cytarabine alone. The IC50values of HAN/cytarabine combination and cytarabine alone were0.16±0.07 μg/mL and0.17±0.09 μg/mL, respectively. DNA fragmentation was also studied, and the exposure of HL-60 cells to cytarabine produced10.70±0.96% DNA fragmentation compared to18.90±1.33% when cells were exposed to combination of cytarabine with HAN. The antimicrobial activity of hippuric acid and HAN nanocomposite was carried out against Gram-positive bacteria, Gram-negative bacteria, and yeasts. It was found thatPseudomonas aeruginosaand methicillin-resistantStaphylococcus aureuswere more sensitive to HAN compared toBacillus subtilisandSalmonella choleraesuis.
Highlights
Metal hydroxide compounds can be classi ed according to their structures and chemical compositions into two groups. e rst group is the layered double hydroxide (LDH) derived from the brucite structure (Mg(OH)2) through substitution part of the divalent cations by the trivalent ones
M21+−xxM3xx+(OH)2(Ammm)xxxxx ⋅ nnH2O), where M2+ is divalent cations, M3+ is trivalent cations, and Ammm is exchangeable anion with a charge (m−) [1]. e second group is the metal hydroxide compounds which are layered metal hydroxide salt (LHS) that can be represented by the general formula (LHS − M2+(OH)2−xx(Ammm)xxxxx ⋅ nnH2O) [2]. e interlayer anion exchangeable capability of LDH and LHS meets the requirement of inorganic layers for encapsulating organic drugs with negative charge and is used in drug delivery applications [3], as well as controlled release systems [4,5,6,7]
Our previous work showed that hippuric acid intercalated into zinc layered hydroxide potentiated the cytotoxicity of tamoxifen against hepatocellular carcinoma HepG2 [9]. e present study was conducted to investigate whether hippurate nanocomposite (HAN) could enhance the toxic effect for cytarabine, another chemotherapy used commonly to treat human promyelocytic leukemia
Summary
Metal hydroxide compounds can be classi ed according to their structures and chemical compositions into two groups. e rst group is the layered double hydroxide (LDH) derived from the brucite structure (Mg(OH)2) through substitution part of the divalent cations by the trivalent ones. E rst group is the layered double hydroxide (LDH) derived from the brucite structure (Mg(OH)2) through substitution part of the divalent cations by the trivalent ones. M21+−xxM3xx+(OH)2(Ammm)xxxxx ⋅ nnH2O), where M2+ is divalent cations, M3+ is trivalent cations, and Ammm is exchangeable anion with a charge (m−) [1]. E second group is the metal hydroxide compounds which are layered metal hydroxide salt (LHS) that can be represented by the general formula (LHS − M2+(OH)2−xx(Ammm)xxxxx ⋅ nnH2O) [2]. E interlayer anion exchangeable capability of LDH and LHS meets the requirement of inorganic layers for encapsulating organic drugs with negative charge and is used in drug delivery applications [3], as well as controlled release systems [4,5,6,7]. A parallel to that, antimicrobial activity of HAN nanocomposite against different micro-organisms was determined
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