title: New approaches in drug treatment for tuberculosis: Inhalation using liposomes only a future vision or soon in clinical practice?
abstract: A major change of therapy in respiratory medicine has been the transition from oral or parenteral to inhalation therapy, for example, in asthma. Inhalation of anti-infectious drugs has however not a key-role in the treatment of pulmonary infections such as tuberculosis (TB). The inhalation therapy provides several benefits; the target is reached directly with evasion of first-pass metabolism, thereby resulting in reduced systemic side effects. Furthermore, the drug is delivered to an extensive surface area that is rich in lymphoid tissue. The inhalation therapy is also easier to monitor since a more direct response is expected than orally administered drugs. Local side effects are, however, common and may depend on inadequate inhalation technique or devices. However, there are problems to consider regarding the delivery of drugs by inhalation: the anatomic structure of the tracheobronchial tree and the impact of the disease on the normal bronchial lining and the mucus. The latter may have an impact on the absorption of the inhaled drug because the mechanical and immunological defense mechanisms play a crucial role for the balance between clearance and absorption. The inhaled drug is expected to be rather effective in the overt presence of bacteria as in smear-positive cases of TB in which the bronchial tree may be directly connected with the cavitary lesions. Such compartments have more rapidly multiplying TB bacteria than other TB-infected compartments. The hypothesis is that the period of contagiousness is expected to be shorter and the recovery faster if there is an intervention directly against the major burden of TB bacteria. The size of the drug particles is essential to overcome the anatomical barriers. To improve the delivery of drugs, they should be in the form of fine particles, that it <5μm in size. Particles sized <2μm can be deposed in the alveoli. To encapsulate drugs for pulmonary delivery in liposomes has several advantages. There will be a prolonged release of the drug in the large surface area of the lungs and a high permeability of the epithelium through the liposome morphology. In general, liposomes are designed as closed spherical vesicles with a wall of a lipid bilayer that encapsulates an aqueous phase in which drugs can be stored. TB treatment with drugs administered by inhalation and liposomes is one future alternative. There are other possibilities for evaluation as well, such as high-dose rifampicin therapy and novel drugs. All new possibilities have to be considered with scientific scrutiny, proper management, and adherence. The clinical community and the patients cannot lose any more opportunities in the management of TB.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, and Angered Hospital, Gothenburg, Sweden. Electronic address: oloflarsolof@gmail.com.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Larsson
keywords: Inhalation therapy; Liposomes; Multiplying tuberculosis bacteria; Tuberculosis treatment