Classical TB Therapy
Clinical management of TB poses several serious questions (Figure 2).
The first obstacle is due to the reduction of the efficacy of chemotherapy. This may be attributed to degradation of the drug before reaching the target, the low levels of cell permeability to drugs or primary drug resistance. Other reasons for the failure of chemotherapy may be the difficulty in achieving adequately high drug concentrations at the infection site, inadequate penetration into macrophages, as well as inadequate penetration into the granulomas, which are as stated, reservoirs of latent bacteria in the host alveolar tissue.[13,24] The treatment of mycobacterial infections is also difficult because, as mentioned, mycobacteria are highly resistant intracellular pathogens.
The TB treatment requires a long period of chemotherapy (6–9 months) with combinations of agents to minimize the emergence of antimicrobial resistance.[24,27] The necessity of an extended period of treatment is a direct result of the lifecycle of the bacilli, some of which may enter into a 'latent' or 'persistent' phase after the initial infections. Hence, the long period of chemotherapy is first to destroy the population of actively multiplying bacilli that can be found initially, and secondly, to prevent reactivation of any latent bacillus present in granulomas that attempts to multiply. Finally, an option that is not usually considered is that the macrophages themselves, following their normal dynamics, drain the bacilli from granulomas towards the outside. Thus, by reducing inflammation and preventing multiplication of the bacilli, antibiotic treatment is also highly recommendable to prevent the continuous formation of FMs and their accumulation or movement through the alveolar spaces.
The most effective pharmacotherapy in TB treatment is a multidrug combination of isoniazid, pyrazinamide and rifampicin. During the initial intensive stage (2 months), these three agents are administered together with ethambutol. The second phase (4 months) comprises exclusively rifampicin and isoniazid. These four drugs, together with streptomycin, make up the so-called first-line therapy. Other drugs (e.g., rifabutin, ethionamide, amikacin, kanamycin A and levofloxacin) have been used in the treatment of TB; however, these are considered as a second-line therapy since these are more toxic, more expensive and less active than first-line agents.
Besides the abovementioned classical therapeutic regimes, new drugs with interest for TB treatment are being developed and they are presently in different steps of preclinical or clinical trials. This issue is out of the scope of this article, but additional information can be found in the following references.[28,30–41]
Although the development of new anti-TB drugs is an obvious approach to fight TB, mechanisms to improve the efficacy of existing drugs can represent a faster strategy. The long and necessary treatment schedules of classical chemotherapy are associated with severe toxic side effects, including hepatotoxicity, and result in poor compliance, one of the main reasons for the emergence of multidrug-resistant pathogens.[15,42] In this regard, improvement of the therapeutic index of existing anti-TB drugs, namely by their encapsulation into nanodelivery systems, should be considered, aiming at maximization of the drug concentration at infected sites, reduction of toxic effects and reduction of treatment duration. Furthermore, the development of nanodelivery systems will provide an opportunity to exploit the inhalatory route, which will be of particular interest in the case of pediatric patients for which most of the first-line drugs are not available.
According to the mentioned disadvantages of classical chemotherapy and to the hope that has been put in a nanotherapeutic approach, this article will provide a state of art in the use of liposomes as nanodelivery systems for the treatment of TB.
Nanomedicine. 2011;6(8):1413-1428. © 2011 Future Medicine Ltd.
Cite this: Liposomes as Drug Delivery Systems for the Treatment of TB - Medscape - Oct 01, 2011.