Nanocarrier-based interventions for the management of MDR/XDR-TB

Abstract

Emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB over the past decade presents an unprecedented public health challenge to which countries of concern are responding far too slowly. Global Tuberculosis Report 2014 marks the 20th anniversary of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance, indicating the highest global level of drug-resistance ever recorded detection of 97 000 patients with MDR-TB resulting in 170 000 deaths in 2013. Treatment of MDR-TB is expensive, complex, prolonged (18-24 months) and associated with a higher incidence of adverse events. In this context, nanocarrier delivery systems (NDSs) efficiently encapsulating considerable amounts of second-line anti tubercular drugs ((s)ATDs), eliciting controlled, sustained and more profound effect to trounce the need to administer (s)ATDs at high and frequent doses, would assist in improving patient compliance and avoid hepatotoxicity and/or nephrotoxicity/ocular toxicity/ototoxicity associated with the prevalent (s)ATDs. Besides, NDSs are also known to inhibit the P-glycoprotein efflux, reduce metabolism by gut cytochrome P-450 enzymes and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. This review first provides a holistic account on MDR-TB and discusses the molecular basis of Mycobacterium tuberculosis resistance to anti-tubercular drugs. It also provides an updated bird's eye view on current treatment strategies and laboratory diagnostic test for MDR-TB. Furthermore, a relatively pithy view on patent studies on second-line chemotherapy using NDSs will be discussed.

New active formulations against M. tuberculosis: Bedaquiline encapsulation in lipid nanoparticles and chitosan nanocapsules

“…Multidrug resistant TB (MDR-TB) and extensively drug-resistant TB strains (XDR-TB, a form of MDR-TB with additional resistance to any of the fluoroquinolones and to at least one of three injectable second-line) have been identified in 105 countries worldwide, and they are making increasingly difficult to successfully treat tuberculosis. Drugs available for the treatment of bacterial infections resistant to antimicrobial drugs are very limited, induce severe side effects and/or are difficult to administer, so they could require parenteral injection [4]. Moreover the high costs of these treatments and their low success rates should be taken into account [5].…”

“…Bedaquiline, a diarylquinoline antimycobacterial drug, the first FDA approved anti-TB drug in four decades, is a very effective drug, nonetheless it shows serious side effects including induction of life-threatening cardiac arrhythmias [5]. Therefore, this drug is to be prescribed only when no other treatment options are available [4,6].…”

Kanamycin Sulphate Loaded PLGA-Vitamin-E-TPGS Long Circulating Nanoparticles Using Combined Coating of PEG and Water-Soluble Chitosan

“…KS is an aminoglycosides (AGs) second-line antimycobacterial agent [1]. KS is considerably a large molecule that is often used in injection form due to poor absorption through the gastrointestinal tract [2].…”

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

“…72,[77][78][79][80][81] The mobility of the bioactive compound is greatly reduced with a solid lipid core, so it remains in the gut, which enhances the sustained release of the compound for a prolonged period of time. Various methods have been used to develop solid lipid nanoparticles, including multiple emulsion, high-pressure homogenization, and ultrasonication.…”