THE CONTROLLED DELIVERY OF DRUGS TO THE LUNG

Inhalation of aerosolised drugs has become a well established modality in the treatment of localised disease states within the lung. However , most medications in aerosol form require inhalation daily at least 3 -4 times because of the relatively short duration of resultant clinica l effects. Some studies have been conducted with a view to sustaining release of drugs in the lung so as to prolong drug action, reduce side effects and improve patient compliance. Liposomes have been shown to have the potential to produce controlled delivery to the lung, since t hey can be prepared with phospholipids endogenous to the lung as surfa ctants. Up to now, many drugs have been incorporated into liposomes an d tested in both human subjects and animal models as pulmonary deliver y systems. Other biodegradable microspheres (MS) such as albumin MS an d poly(lactide and/or glycolide) copolymer MS are also being investiga ted. In contrast to liposomes, these MS may be more physico-chemically stable both in vitro and in vivo. Thus, drugs entrapped in biodegrada ble MS may have a slower release rate and a longer duration of action than those incorporated in liposomes. The prodrug approach has been su ccessful in producing long-lasting bronchodilators whilst conjugation of drugs to macromolecules provides a possible mechanism for controlle d release of drugs for either localised or systemic actions, Sustained release in the lung can also be achieved by reducing the aqueous solu bility of the drug or co-precipitating relatively insoluble materials with aqueous soluble drugs. In contrast, inclusion of drugs in cyclode xtrins is unable to sustain drug release in the lung, which may be due to the premature breakdown of drug-cyclodextrin conjugates in vivo. M any interdependent factors, involving the lung, carrier, drug and devi ce have been shown to influence the overall disposition of drugs in th e respiratory tract after inhalation. Current studies on pulmonary del ivery systems have many limitations, mainly due to the lack of suitabl e animal models and the chronic side effects of drug carriers have yet to be established. Thus, more inter-disciplinary collaboration is ess ential for the development of effective controlled drug delivery syste ms intended for administration to the lung.