# Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance
## 6 Investigative Strategies to Eradicate Biofilms
### Nanoparticle Systems  
Owing to the poor permeability concerns coupled with the available drugs towards the persister cells, nanoparticle (NP) delivery systems can be explored for localized drug delivery of antimicrobial agents into biofilms. As evident by several reports, silver nanoparticles (AgNPs) have intrinsic bactericodal property and are proven to eradicate biofilms. [PERSON] et al. studied AgNPs and evaluated their biofilm inhibition against two strains of _K. pneumoniae_. The percent biofilm inhibition was found to be 64% and 86% for _K. pneumoniae_ MP953600 and MP953599, respectively at 100 ug/mL concentration [231]. Additionally, the formation of EPS was reduced on treatment with AgNPs and caused cellular membrane disruption. In a similar work by [PERSON] et al. the biofilm inhibitory activity and antivirulence ability of AgNPs was assessed towards multidrug-resistant _A. baumaniii_. The results showed a downregulation in expression of virulence and biofilm-related genes like _afa_/_draBC_, _kpsMI_, _ompA_, _bap_, and _csuA_/_B_ by AgNPs [232]. Recently, [PERSON] et al. studied synthesis of Ag and Au NPs from _Cannabis sativa_ and explored their biofilm inhibitory effect towards _P. aeruginosa_ and _E. coli_ at a concentration range of 1.6-100 ug/mL. AgNPs displayed superior inhibition of biofilm formation even at sub-MIC level [233].  
[PERSON] et al. recently designed tailor-made mesoporous silica NPs as a carrier for the antibiotic vancomycin using surface functionality like amine, carboxyl or aromatic groups. The cellular affinity and attachment with mesoporous silica NP suspensions 0.25 mg/mL was related to a decrease in growth of MRSA biofilm cells [234; 235].  
A new nanohybrid complex of Ag and iron oxide was designed and subjected to a magnetic field by [PERSON] et al. These magnetically responsive NPs responded remarkably well compared to bare nanohybrid complexes in disrupting biofilms of _E. coli_ and _P. aeruginosa_ with inhibitions of 88% and 90%, respectively [236; 237]. [PERSON] et al. designed a thermoresponsive glycol chitin-based nanocomposite composed of iron oxide nanoparticles and D-amino acids, which transformed from a solution to a gel at physiological temperature with release of D-amino acids. Following the initial disruption by D-amino acids, the nanocomposites combined with thermal treatment were actuated by an external magnetic field to achieve complete disruption of _S. aureus_ biofilms [238; 239]].  
The intricacy in the structure of the biofilms makes the antibiotics difficult to target the bacteria and emergence of resistance to them. Unlike traditional antibiotics, NPs have peculiar dimensions of <100 nm, making them an apt carrier for the antibiotics. These NPs due to their size, help to selectively target the antibiotics to the infestation site thereby lowering the detrimental systemic adverse effects. The NPs exhibit their antimicrobial activity fundamentally by following mechanisms like disrupting the cell membrane and generating ROS. The ROS sequentially initiate intracellular effects by interacting with DNA, ribosomes, enzyme causing oxidative stress associated protein denaturation, DNA damage, ribosomal disassembly and inhibiting cell-to-cell communication within the cell (Figure 14). AgNPs have been shown to induce neutralization of the bacterial membrane surface charges thereby altering its penetrability, eventually leading to cell apoptosis [240; 241].