Addressing Antimicrobial Resistance Through Nanoantibiotics: Challenges and Novel Strategies

Introduction

Infectious diseases caused by pathogenic bacteria's are a leading cause of morbidity and mortality among all ages. The severity of the infection varies from mild inflammation to a catastrophic epidemic. Cholera, dysentery, gonorrhea, measles, meningitis, necrotizing fasciitis, pneumonia and tuberculosis are some of the most severe bacterial infections that have ravaged humanity and had changed the course of history. Many microbial pathogens have evolved diverse escape strategies to surpass the anatomical defenses of the immune system and develop intracellular infections. Through the circulatory system, contagious bacteria spreads inside the body, multiplies, colonizes, and sustains itself, making them difficult to eradicate. Thus, these bacterial infections turn into a life-threatening condition at this stage. Most often, macrophages and other immune cells present in the body's major immune organs, such as bone marrow, lymph nodes, spleen and thymus, involves in the elimination of pathogens from the bloodstream (Infection, n.d.). However, antibiotic treatment is the only viable approach to destroy and inhibit the further growth of deadly pathogenic bacteria. Antimicrobials typically kill bacteria by hampering cell wall synthesis or inhibit vital cellular / metabolic activities in the bacterial metabolism. For example, beta-lactams, glycopeptides and lipopeptides class of antibiotics inhibit bacterial cell wall synthesis; sulfonamides inhibit folic acid synthesis, aminoglycosides, chloramphenicol, macrolides, streptogramins, tetracyclines inhibit protein synthesis; ansamycins inhibit the RNA production, and quinolones interfere with DNA replication and transcription of bacteria cells (A Brief Overview of Classes of Antibiotics, n.d.). Although antimicrobial development has advanced considerably, many bacterial infections remain hard to treat. Some major reasons include poor absorption/diffusion, rapid renal clearance, poor solubility and toxicity to host cells (Jijie et al., 2017). Another most serious and critical issue in treating bacterial infections today is the rapid acquisition of resistance to the antibiotic by the infectious microbes. Unfortunately, antimicrobial resistance (AMR) is now a pandemic at an ever-increasing pace. Many bacteria are entirely resistant to commonly prescribed first-line broad-spectrum antibiotics such as amoxicillin, clarithromycin and erythromycin, resulting in relapse and treatment failure due to recurrence of infection. Recent reports on bacterial resistance to carbapenems and colistin, considered to be last-line antibiotics, are worrying.(). Many of the antibiotics prescribed for decades have been derived primarily from another microbial source which makes it easy for the microbes to acquire resistant mechanisms. Many of the antibiotics prescribed for decades have been derived primarily from another microbial source, making it easy for microbes to acquire resistant mechanisms. In addition, as a result of natural selection, virulence gene transfer through horizontal gene transfer mechanism, environmental stress, and artificial gene transformation practices, the microbes have quickly gained resistance and had now evolved into a multi-resistant superbug. Other factors contributing towards the rise and spread of antibiotic resistance include inappropriate use of antibiotics, failure to complete prescribed antibiotic courses, overuse of antibiotics in forestry, cattle, poultry and fish farms, lack of measures to control infections, poor environmental hygiene, and lack of discovery and development of new antibiotics (Nagarajan et al., 2018). In order to overcome the ill effects and spread of AMR, it is necessary to adopt revolutionary approaches and develop novel antimicrobial therapy and formulation with minimal side effects and improved pharmacokinetic profiles. Antibiotics loaded nanoparticles are one such proposed alternative antimicrobial drug system. Nanoantibiotics (nAbts) offers a unique way of circumventing the existing antibiotic discovery approach and provides a new attack mechanism which can contribute to a longer-term solution for the evolution of drug resistance. It offers environment-specific activation, thus improves the efficacy of the nAbts and also open up new design approaches for various other clinical applications. These nAbts hold a promising future in combating multidrug resistance. However, there is still plenty of efforts required for their successful development into a therapeutic aid for addressing antimicrobial-resistant infections. These "Nanoantibiotics" facilitate to alter and enhance the pharmacokinetic and therapeutic profile of antibiotic drugs, in contrast to the drugs in its free form (). The multiple benefits upon employing nanocarriers include; targeted drug delivery, sustained drug release, enhanced solubility, improved bioavailability, delivery of multiple therapeutic agents for polytherapy and several others, which is also applicable to antimicrobial nanosystems (). Therefore, the nanoantibiotic constructs hold a huge promise to prioritize disease-specific bactericidal treatment at a lower dose to ensure safety with sustained immunity and may hopefully revolutionize the field of nanobiomedicine.