A review of emerging trends in the treatment of tuberculosis

Figures & data

Table I. Species of Mycobacteria that cause tuberculosis.

Organism of mycobacteria	Disease	Host
M. tuberculosis	Tuberculosis	Diseased persons
M. bovis	Intestinal or tonsillar	Diseased cows
M. avium	Disseminated infections	No virulence in normal host
M. intracellular	Disseminated infections	Patients with AIDS

Figure 1. Transmission of tuberculosis.

Table II. Rate of tuberculosis cases by race/ethnicity in United States.

Race/ethnicity	Percent rate (2012)	Percent rate (2013)
Hispanic	5.3	5.0
Black	5.8	5.3
Asian	18.7	18.7
White	0.8	0.7
Other	4.4	3.7

Table III. Classification of antitubercular drugs.

First-line oral anti -TB drugs	Injectable anti-TB drugs	Newer second line drugs (Flouroquinolones)	Oral second line anti-TB drugs	Drugs with unclear function in the treatment of drug resistant TB
Isoniazid	Streptomycin	Levofloxacin	Thiacetazone	Clofazimine
Pyrazinamide	Kanamycin	Ciprofloxacin	P-amino salicylic acid	Linezolid
Ethambutol	Amikacin	Oflaxacin	Ethionamide	Thioacetazone
Rifampicin	Capreomycin	Moxifloxacin	Cycloserine	Clarithromycin
Streptomycin	Vincomycin	Gatifloxacin

Table IV. Side effects of Anti TB drugs.

Anti-tubercular drugs	Side effects
Isoniazid	Rash, Seizure, loss of memory, injury of lungs, stinging pain in feet
Rifampicin	Less appetite, low urine excretion
Pyrazinamide	Pains in joints, pain in abdomen
Ethambutol	Reduced visual quality
Streptomycin	Irritating sensation, loss of memory
Thioacetazone	Skin inflammation
Kanamycin	Toxicity in kidney
Amino salicylic acid	Extreme sensation in body

Table V. Salient features of drug carriers.

S.No.	Carrier	Features
1)	Liposome	Organized from physiological lipids, effectively target macrophages, developed as cargo carriers for cell and organ- specific targets using ligands, have a short shelf life
2)	Nanoparticles	Drug carriers, systemic and pulmonary bioavailability, show good high drug encapsulation
3)	Microparticles	Show low encapsulation for some drugs, show good pulmonary deposition, targeted drug delivery, systemic bioavailability shown to be low following inhalation
4)	Solid lipid nanoparticles	Show high drug encapsulation, show good systemic and pulmonary bioavailability, have a high shelf life
5)	Microspheres	Good drug encapsulation, effective and sustained target delivery

Table VI. Outcomes of liposome-based drug delivery systems in the treatment of TB.

Delivery system	Route of administration	Drug used	Inferences
Liposomes	Aerosol	Rifampicin	Improved delivery of rifampicin to macrophages. To reduce rifampicin side effects by pressurized packed liposomes for pulmonary targeting of drugs (Vyas et al. 2004)
Liposomes phosphatidyl glycerol, cholesterol, and phosphatidyl Choline	Intravenously	Streptomycin	Improved antimicrobial activity against Mycobacterium avium (Gangadharam et al. 1991)
Liposomes	Respiratory	Isoniazid and Rifampicin	Sustained drug release, prevent from irritation formed locally, minimize toxicity (Garg et al. 2012a)
Liposomes	Intravenously	Gentamicin	Decreased CFU count was observed both in spleen and liver after administration of gentamicin-containing liposomes to the infected mice; reduction in bacterial count was related to dose (Klemens et al. 1990)
Liposomes	Intravenously	Pyrazinamide	High therapeutic efficacy was observed in M. tuberculosis-infected mice, when PZA liposomes were injected twice weekly (El-Ridy et al. 2007)

Figure 2. Mechanisms of nanoparticle-based antimicrobial drug delivery to microorganisms: (A) Nanoparticles combine with microbial cell wall or membrane and discharge the transported drugs within the cell wall or membrane; (B) nanoparticles attach to the cell wall and serve as a drug store to continuously release drug particles, which will distribute into the interior of the microorganisms.

Table VII. Outcomes of nanoparticle-based drug delivery systems in the treatment of TB.

Delivery system	Route of administration	Drug used	Inferences
Lectin nanoparticles	Oral	Rifampin Isoniazid Pyrazinamide	Lectins facilitate better mucoadhesion of drug due to bio recognition of the lectin-bound carriers by glycosylated structures in the intestine, thereby increasing the bioavailability (Gabor et al. 2004)
Alginate nanoparticles	Oral	Rifampin Isoniazid Pyrazinamide Ethambutol	Alginate is authorized by the USFDA and is administered orally for treatment of reflux esophagitis. Alginate nanoparticles elevate drug payload, provide better pharmacokinetics, and increase therapeutic efficiency (Goyal et al. 2013b)
PLG(Poly-lactide-co-glycolide) Nanoparticle	Oral	Rifampicin, Isoniazid, Pyrazinamide, Ethambutol.	Increased bioavailability, enhanced pharmacodynamics (Pandey et al. 2003)
Lectin-functionalized PLG nanoparticles	Aerosol	Isoniazid Rifampin Pyrazinamide	Decrease the drug dosage frequency and lead to better patient compliance (Sharma et al. 2004)
Lectin nanoparticle	Subcutaneous	Isoniazid Rifampin Pyrazinamide	Nanoparticles released from the solid dosage forms with their original properties (Gelperina et al. 2005)

Table VIII. Outcomes of microparticle/microsphere-based drug delivery systems in the treatment of TB.

Delivery system	Route of administration	Drug used	Inferences
Microparticles	Inhalation	Isoniazid Rifabutin	Enhance efficacy of anti-tubercular drugs by uptake of inhaled particles by lung macrophages (Parnami et al. 2013)
Alginate Microparticles	Oral	Isoniazid Rifampicin Pyrazinamide	Nine-fold enhancement in bioavailability compared with free drugs (Qurrat ul et al. 2003)
Microspheres	Inhalation	Rifampin	Reduce undesirable side effects of antitubercular drugs by potent pharmacological effects. Reduce hepatic accumulation (Barrow et al. 1998)
PLGA Microspheres	Aerosol	M.TB antigen 85B	Made use of in pulmonary delivery of tuberculosis vaccine. PLGA particles for release of vaccines to stop M. tuberculosis infection (Lu et al. 2007)
Microspheres	Sustained release	Rifampin	Decreasing intracellular M. tuberculosis increment compared to free drug given as equivalent doses of rifampin. Target the delivery of efficient doses of rifampin to macrophages. No patient compliance problem, because dosing is routine and the levels in blood are preplanned (Pandey and Khuller 2005a)
PLGA microspheres	Local	Ofloxacin	For bone tuberculosis (Suarez et al. 2001)

Table IX. Outcomes of solid lipid nanoparticle based drug delivery systems in the treatment of TB.

Drug delivery	Route of administration	Drug used	Inferences
Solid lipid nanoparticles (stearic acid)	Nebulization	Rifampicin, Isoniazid, Pyrazinamide	Improved residence time, improved drug bioavailability, reduced administration rate (Pandey and Khuller 2005b)
Solid lipid nanoparticles	Oral	Rifampicin, Isoniazid, Pyrazinamide	Reduce the dosing frequency and promote better patient compliance (Pandey et al. 2005)
Solid lipid nanoparticles	Inhalation	Rifampicin, Isoniazid, Pyrazinamide	Higher relative bioavailability as compared to conventional drug delivery (Ahmad et al. 2005)
Solid lipid nanoparticles	Insufflation	Capreomycin sulfate	The plasma concentrations of capreomycin were higher 2 h after i.v. (Garcia-Contreras et al. 2007)
Solid lipid nanoparticles	Dry powder inhaler	Rifampicin	In vitro drug release was found to be for 6 days, and a significant decrease was observed in the number of CFUs at 7 days in M. tuberculosis H37Rv infected cell lines, upon bioassay assessment of cell culture obtained from monocyte cell lines (Kaur et al. 2014a)

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