Alginate-Capped Silver Nanoparticles as a Potent Anti-mycobacterial Agent Against Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) is a leading cause of death from a single infectious agent, Mycobacterium tuberculosis (Mtb). Although progress has been made in TB control, still about 10 million people worldwide develop TB annually and 1.5 million die of the disease. The rapid emergence of aggressive, drug-resistant strains and latent infections have caused TB to remain a global health challenge. TB treatments are lengthy and their side effects lead to poor patient compliance, which in turn has contributed to the drug resistance and exacerbated the TB epidemic. The relatively low output of newly approved antibiotics has spurred research interest toward alternative antibacterial molecules such as silver nanoparticles (AgNPs). In the present study, we use the natural biopolymer alginate to serve as a stabilizer and/or reductant to green synthesize AgNPs, which improves their biocompatibility and avoids the use of toxic chemicals. The average size of the alginate-capped AgNPs (ALG-AgNPs) was characterized as nanoscale, and the particles were round in shape. Drug susceptibility tests showed that these ALG-AgNPs are effective against both drug-resistant Mtb strains and dormant Mtb. A bacterial cell-wall permeability assay showed that the anti-mycobacterial action of ALG-AgNPs is mediated through an increase in cell-wall permeability. Notably, the anti-mycobacterial potential of ALG-AgNPs was effective in both zebrafish and mouse TB animal models in vivo. These results suggest that ALG-AgNPs could provide a new therapeutic option to overcome the difficulties of current TB treatments.

Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats

“…The irradiated alginate, as a stabilizing agent, provided a negative surface charge with sufficient interparticle repulsion (zeta potential = −32.0 mV) against spontaneous agglomeration. Previously, alginate-stabilized AgNPs have been synthesized using plasma-activated water ( 35 ) and glucose reduction methods ( 36 ), but at larger particle sizes of approximately 22 and 70 nm, respectively. However, the glucose reduction method showed better suspension stability with zeta potential at -47 mV at alginate concentration of 0.5% (w/v) than the other nanoparticles ( 36 ).…”

Impact of nanoparticles on amyloid β-induced Alzheimer’s disease, tuberculosis, leprosy and cancer: a systematic review

“…Furthermore, the patient incompliance and the drug resistance phenomenon (both multidrug-resistance, MDR/extensively drug-resistance, XDR) adds a bit more complexity for the treatment of tuberculosis. The current approach of nanotechnology involves greater prospect to be utilized for the treatment of TB, by preparing different nanoformulations which is yet to be explored [ 81 ]. The primacy of this therapeutic approach have several features: (i) efficient carrying capacity, (ii) more time span activity, (iii) facile route of administrations, (iv) loading of various drugs or easy encapsulations and (v) lower toxicity towards the host cells [ 82 ].…”

“…Attempts have also been made to study the inhibitory effect of silver nanoparticles towards drug resistant (both MDR and XDR) M. tuberculosis strains. Chen et al explored the anti-mycobacterial activity of synthesized AgNPs [where alginate (ALG) was utilized as a capping agent] against numerous pathogenic mycobacterial strains which includes both drug-sensitive and drug-resistant strains (MDR and XDR strains) [ 81 ]. It was concluded from this study that alginate capped silver nanoparticles (ALG-AgNPs) inhibited the growth of above mentioned mycobacterial strains, without conferring any toxicity to the THP1 cells.…”

“…Fluorescence-based cell permeability experiment revealed that ALG-AgNPs treatment increases the cell permeability which may be the possible mechanism behind its anti-mycobacterial activity. The therapeutic effect of ALG-AgNPs was further assessed by executing the in vivo studies on zebrafish and mouse TB model which unveiled that the bacterial load was reduced upon the treatment of these nanoparticles without causing any cytotoxicity in the host cell [ 81 ]. Even, silver containing mesoporous silica-based nanosystems (MSNs-AgBrNPs and Ag@MSNs) have growth inhibitory effects [ 87 ].…”

Alginate‐Based Nanosystems for Therapeutic Applications

“…For latent TB, oxygen-limiting conditions were imposed upon the H37Rc strain, inoculated with 25 μg/ml, 50 μg/ml, and 100 μg/ml of the nanocomposites. Under a persistent nonreplicating state, colonial growth was prevented as the cells were coerced into becoming dormant, whereas this observation was repealed when compared to the PBS-treated hypoxic environment [36].…”