pH-Triggered Controllable Release of Silver–Indole-3 Acetic Acid Complexes from Mesoporous Silica Nanoparticles (IBN-4) for Effectively Killing Malignant Bacteria

Abstract

An efficient approach for the antimicrobial agent delivery specifically at acidic pH has been proposed. At the outset, functionalized mesoporous nanoparticles (NPs) were examined to verify the success of synthesis while considering the structural properties by various characterizations. The NPs were immobilized with silver-indole-3 acetic acid hydrazide (IAAH-Ag) complexes via a pH-sensitive hydrazone bond, which functioned as a model drug. When the transitional metal complexes with IBN-4-IAAH-Ag were exposed to acidic pH (near pH 5.0), the silver ions were preferentially released (70%) in a controlled manner up to 12 h by pH-sensitive denial of hydrazone bonds. In contrary, a low drug release (about 25%) was seen in physiological buffer (pH 7.4) demonstrating the pH sensitive release of this drug. Furthermore, the antibacterial efficacy of this unique structured sample was tested against the planktonic cells and biofilms of Gram-positive and Gram-negative bacteria with field emission scanning electron microscope in turn measuring the growth curves, formation of lethal reactive oxygen species, protein leakage, and DNA damage. The synthesized pH-sensitive IAAH-Ag complex was found to have high antimicrobial efficacy against multidrug resistant clinical isolates both in planktonic and biofilm states. Going forward, the synthesized nanoconjugates proved a good in vivo efficacy in treating the bacterial infection of mice. These new metal complex-conjugated NPs through a pH-sensitive hydrazone bond opened up a new avenue for the design and synthesis of the next generation antibacterial agents, which would act as an alternative to antibiotics.

Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles

“…It is well known that bacterial infection is accompanied by local decrease in pH, which is induced by generation of several organic acids triggered by low-oxygen condition. 37,38 Therefore, acidic microenvironments were used as a trigger for accelerated CHX release. As shown in Figure 3A, there was an initial burst in the first 12 hours.…”

Untitled

“…Similarly, by using the above procedure 10 new derivatives i.e (3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J) were prepared and their structure was established on the basis of elemental analysis and spectral data. The required indole 3 acetic acid hydrazine(4) is prepared by procedure as describe in literature 16 0.001 Mole of indole 3 acetic acid was dissolved in 100 ml absolute ethanol. 3 drops of sulphuric acid were added and refluxed for 18 hours.…”

“…After completion of reaction content was neutralized with NaHCO 3 (Esterification reaction) filtered it to remove the salt, after that 0.003 mole hydrazine hydrate was added to above Ester and refluxed for 15 hours. Product was obtained by filtration and recrystallized it from ethanol to give pure compound [16][17][18][19] . As white solid (75% yield); mp = 142˚C; IR: (KBr cm (2,4 dichloro phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-(3H-indol-3-yl) amino phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-(3H -indol -3-yl …”

Mesoporous Silica‐Based Materials with Bactericidal Properties

“…Other MS NPs which released Ag(I) were also prepared by Lee and co‐workers . The nanoparticles were first functionalized with butylaldehyde and then, indole‐3‐acetic acid hydrazide was grafted through the formation of imine bonds with the previously anchored aldehyde.…”