Present status of nanoparticle research for treatment of Tuberculosis

Shegokar, Ranjita; Shaal, Loaye Al; Mitri, Khalil

doi:10.18433/j3m59p

Cited by 66 publications

(38 citation statements)

References 108 publications

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“…8 They act as effective drug delivery carriers and help in increasing drug bioavailability and reducing dosing frequency. 9,10,11,12,13,14,15 Metallic nanoparticles such as silver and oxides of metals, including zinc and titanium, themselves are antimicrobial nanomaterials. 8,16 When these 4 nanoparticles are used along with antibiotics, an additive or synergistic effect is observed on bacterial growth inhibition.…”

Section: Introductionmentioning

confidence: 99%

Polyacrylic Acid-Coated Iron Oxide Nanoparticles for Targeting Drug Resistance in Mycobacteria

2014

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The emergence of drug resistance is a major problem faced in current tuberculosis (TB) therapy, representing a global health concern. Mycobacterium is naturally resistant to most drugs due to export of the latter outside bacterial cells by active efflux pumps, resulting in a low intracellular drug concentration. Thus, development of agents that can enhance the effectiveness of drugs used in TB treatment and bypass the efflux mechanism is crucial. In this study, we present a new nanoparticle-based strategy for enhancing the efficacy of existing drugs. To that end, we have developed poly(acrylic acid) (PAA)-coated iron oxide (magnetite) nanoparticles (PAA-MNPs) as efflux inhibitors and used it together with rifampicin (a first line anti-TB drug) on Mycobacterium smegmatis. PAA-MNPs of mean diameter 9 nm interact with bacterial cells via surface attachment and are then internalized by cells. Although PAA-MNP alone does not inhibit cell growth, treatment of cells with a combination of PAA-MNP and rifampicin exhibits a synergistic 4-fold-higher growth inhibition compared to rifampicin alone. This is because the combination of PAA-MNP and rifampicin results in up to a 3-fold-increased accumulation of rifampicin inside the cells. This enhanced intracellular drug concentration has been explained by real-time transport studies on a common efflux pump substrate, ethidium bromide (EtBr). It is seen that PAA-MNP increases the accumulation of EtBr significantly and also minimizes the EtBr efflux in direct proportion to the PAA-MNP concentration. Our results thus illustrate that the addition of PAA-MNP with rifampicin may bypass the innate drug resistance mechanism of M. smegmatis. This generic strategy is also found to be successful for other anti-TB drugs, such as isoniazid and fluoroquinolones (e.g., norfloxacin), only when stabilized, coated nanoparticles (such as PAA-MNP) are used, not PAA or MNP alone. We hence establish coated nanoparticles as a new class of efflux inhibitors for potential therapeutic use.

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Section: Introductionmentioning

confidence: 99%

Polyacrylic Acid-Coated Iron Oxide Nanoparticles for Targeting Drug Resistance in Mycobacteria

2014

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“…Improved bioavailability is achieved with less dose as compared to other drug delivery system [44]. Thus, efficient therapy is achieved with reduced side effects and toxicity [45]. For PDD of ATDs various nanocarrier systems as Vesicle-based, lipid based, emulsion based, and polymer based are formulated and tested [46].…”

Section: Need Of Pdd Of Nps Containing Atdsmentioning

confidence: 99%

Drug-Resistant Tuberculosis: Recent Approach in Polymer Based Nanomedicine

Shaji

Shaikh

2016

Int J Pharm Pharm Sci

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Tuberculosis (TB) had been a leading chronic bacterial infection since decades. Current therapeutic management of Mycobacterium tuberculosis (MTB) is inadequate due to the lengthy course of treatment, drug-related side effects and ill-planned therapy, and these factors can lead to therapeutic failure and the emergence of drug-resistant TB. The Multi-drug-resistant (MDR) TB needs a lengthy course of treatment with secondline antitubercular drugs (ATDs) having higher side effects and cost. The misuse of second-line ATDs may result in extremely drug-resistant (XDR) strain which is very difficult to treat and require high doses of drugs resulting in more toxicity and side effects. This review highlights the need for novel drug delivery for the treatment of drug-susceptible and resistant TB. The characteristics of the nanoparticulate system in ATDs delivery and its approach in the MDR and XDR TB are discussed. The lung is the site of infection in pulmonary TB and the targeted drug delivery to the site of infection helps in achieving increased efficacy with less dose further reducing the side effects and toxicity. The symbiotic association of nanotechnology and pulmonary drug delivery give rise to an efficient inhalable polymer based nanoparticulate system containing ATDs for the better management of drug-susceptible and resistant TB. Various ATDs loaded polymer based nanocarrier systems like Alginate, PLGA, Chitosan and Gelatin nanocarriers are discussed in detail. Thus, this review highlights the current research in pulmonary drug delivery of polymer based ATDs nanomedicine and their importance in control of drug-resistant TB.

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“…Due to high incidence of side effects and the long treatment, a patient's adherence is low and this results in relapse of symptoms causing an alarming increase in the prevalence of multi-drug resistant (MDR) TB. Additionally, few drug molecules actually reach the lung alveoli, the desired site for drug action [5].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria

Bhave

Ghoderao

Sanghavi³

et al. 2013

Adv. Nat. Sci: Nanosci. Nanotechnol.

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Tuberculosis (TB) is one of the most critical infectious diseases affecting the world today. Current TB treatment involves six months long daily administration of four oral doses of antibiotics. Due to severe side effects and the long treatment, a patient's adherence is low and this results in relapse of symptoms causing an alarming increase in the prevalence of multi-drug resistant (MDR) TB. Hence, it is imperative to develop a new drug delivery technology wherein these effects can be reduced. Rifampicin (RIF) is one of the widely used anti-tubercular drugs (ATD). The present study discusses the development of biocompatible nanoparticle-RIF complexes with superior inhibitory activity against both Mycobacterium smegmatis (M. smegmatis) and Mycobacterium tuberculosis (M. tuberculosis). Iron oxide nanoparticles (NPs) synthesized by gas phase condensation and NP-RIF complexes were tested against M. smegmatis SN2 strain as well as M. tuberculosis H37Rv laboratory strain. These complexes showed significantly better inhibition of M. smegmatis SN2 strain at a much lower effective concentration (27.5 µg ml −1 ) as compared to neat RIF (125 µg ml −1 ). Similarly M. tuberculosis H37Rv laboratory strain was susceptible to both nanoparticle-RIF complex and neat RIF at a minimum inhibitory concentration of 0.22 and 1 µg ml −1 , respectively. Further studies are underway to determine the efficacy of NPs-RIF complexes in clinical isolates of M. tuberculosis as well as MDR isolates.

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Present status of nanoparticle research for treatment of Tuberculosis

Cited by 66 publications

References 108 publications

Polyacrylic Acid-Coated Iron Oxide Nanoparticles for Targeting Drug Resistance in Mycobacteria

Polyacrylic Acid-Coated Iron Oxide Nanoparticles for Targeting Drug Resistance in Mycobacteria

Drug-Resistant Tuberculosis: Recent Approach in Polymer Based Nanomedicine

Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria

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