The worldwide misuse of antimicrobials and subsequent rise of the multi-drug resistant (MDR) opportunistic intracellular pathogens have led to a paradigm shift in the established perspective of antimicrobials and bacterial-human relations. Antibiotic resistant strains of mycobacterium tuberculosis have threatened the progress in management and control of worldwide epidemic of tuberculosis. Mycobacterium tuberculosis intrinsically resists many antimicrobials, limiting the number of compounds available for treatment. Typically, conventional treatments for these diseases consist of long-term therapy with a combination of bioactive(s) that can cause side effects and contribute to low patient compliance. The escalation of antimicrobial resistance poses compelling demand for new ways of treating bacterial infections. The main objective of this chapter is to review the potential applications of nanotechnology-based drug delivery systems in combating drug resistance associated with opportunistic intracellular pathogens with special reference to tuberculosis.
TopIntroduction
Tuberculosis (TB), an ancient human scourge, is an increasing health illness in both the developing and developed world. It is a dreadful health challenge that primarily affects the respiratory system. It is a communicable disease and one among the top 10 leading infectious killers in the world(MacLean et al., 2019). It is considered alongside HIV as the global menace.The pathogenic bacterial species responsible for TB is Mycobacterium tuberculosis.It spreads through the infected person who expels bacteria into the air, e.g. by coughing.The frequently affected organ is the lungs wherein it is manifested as pulmonary TB and it might spread to other organs causing extrapulmonary TB(Sharma & Mohan, 2019).A quarter of the world’s population including both developing and developed countries are affected by Mycobacterium tuberculosis and therefore at greater risk of developing TB. As per the WHO report 2019, approximately 1.2 million deaths from TB among HIV-negative people and an additional 251000 deaths among HIV positive people were reported in 2018. People of both sexes are affected by TB among all age groups. However, the high TB burden is recorded in men (aged≥15 years) that represents 57% of all TB cases in 2018. In contrast to the fact, women only accounted for 32% and children (< 15 years of age) for 11%. 8.6% of all TB cases in HIV-positive people. Most of the TB cases were identified by WHO in the vicinity of South East Asia (44%), Africa (24%) and the western Pacific (18%), eastern Mediterranean (8%), America (3%), and Europe (3%). 2/3 rd of the global TB burden was identified in following countries: India (27%), China (9%), Indonesia (8%), Philippines (6%), Pakistan (6%), Nigeria (4%), Bangladesh (4%) and South Africa (3%). These and along with 22 other countries as per WHO’s list of 30 high TB burden countries were found to have for 87% of total reported cases globally (World Health Organization, 2019).
Drug-resistant TB continues to pose a threat to human beings worldwide. The escalation in bioactive resistant strains involves multiple factors: poor public healthcare facilities (e.g., delay in the diagnosis of bioactive resistance, treatment interruptions, the inconsistent supply of anti-tubercular bioactive(s)), incomplete therapy (e.g., unmonitored therapy, non-adherence by patients, inappropriate or incorrect use of anti-tubercular bioactive(s)), and low immunity due to HIV infection. Several first and second-line anti-tubercular bioactive(s) have been developed against Mycobacterium tuberculosis (Jnawali & Ryoo, 2013). The mechanism of antimicrobial action of these bioactive(s) is used against causative pathogen i.e., Mycobacterium tuberculosis. Globally, a more alarming and recent public health threat has arisen after the identification of multidrug-resistant tuberculosis (MDR-TB) (Nyang'wa et al., 2019). In MDR-TB the mycobacterial strain is resistant to Isoniazid and Rifampicin, the two most powerful anti-tubercular bioactive(s), thus consequent upon a severe threat to conventional anti-tubercular treatment. The DOTs therapy (current conventional therapy) addresses this hurdle through a complex and prolongs treatment involving a combination of high dosage of bioactive(s) which are associated with side effects. Novel drug delivery modules (nanocarriers) are potentially seen as an option for the treatment of drug-resistant tuberculosis that can conquer the limitations of conventional anti-tubercular therapy. Anti-tubercular bioactive(s) entrapped or encapsulated in these nanocarrier systems leads to higher bioavailability. When these nanobiomaterials coupled to a targeting moiety, it may result in significantly boosted the drug efficacy with less or no drug-associated side effects (Mehta et al., 2019; Hamed et al., 2019). This chapter discusses the recent developments in the understanding of the mechanism of antibiotic resistance in tuberculosis with special reference to MDR-TB and also covers the applications and advantages of nanocarrier based anti-tubercular drug delivery systems to circumvent drug-resistant tuberculosis.