Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems

Abstract

Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists' interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.

Keywords: antimicrobial resistance; drug delivery; lipid-based nanocarriers; microfluidics; nanoparticles; resistance mechanism.

Figure 1

Mechanisms illustrating antibiotics resistance strategy used by bacteria. A Gram-negative bacterium is depicted various mechanisms for antibiotics resistance approaches against different antimicrobial agents are specified. (1) Hindering of antibiotics’ entry and removal using efflux pump. (2) Transformation of drug either by degradation or by changing drugs’ original confirmation. (3) Modification of antibiotics’ target by gene mutation. (4) Diversion of pathway containing drug target. (5) Horizontal transfer of gene.

Figure 2

Mechanism of bacterial superbug formation by acquiring multiple drug resistance plasmid through horizontal gene transfer.

Figure 3

Multiple pathways followed by advanced nanotechnological approaches to combat the antibiotic resistance.

Figure 4

The illustration shows the role of drug-loaded nanocarrier in inhibiting the antibiotic resistance by internalizing into the DNA bases, inhibiting cell wall synthesis, suppressing ribosomal units, and by increasing the permeation through cell membrane.

Figure 5

Inorganic nanoparticles and their mode of antibacterial mechanism.

Figure 6

Microfluidic chips for microbiome purification, detection and downstream analysis. (A) Image of the custom designed MiSens biosensor with exploded view of the chip design. The fully automated microfluidic-based sensor was used for real-time bacteria detection. (Reproduced with permission from [139]). (B) Schematic illustration of the microfluidic chip for E. coli detection. (i) The PDMS chip contained two parallel microfluidic chips for DNA detection and negative control. The microfluidic chip composed of a reaction chamber, an active valve, an electrode chamber to provide 66 °C of heat, glass slide as the substrate and PDMS chip. (ii) Photograph of the chip with two parallel microfluidic channels with capillary tubes to connect the chip to the syringe pump. (iii) Micrograph of the chip. (Reproduced with permission from [157]). (C) (i) Schematic illustration of the microfluidic chip to capture bacteria by inertial focusing. (ii) Dean vortices in action in a channel with trapezoid cross-section. (iii) Photograph of the 3D printed device. (Reproduced with permission from [158].