Nanoaerosolized Drugs and Insecticides

 

Many commercial devices for treatment of asthma, tuberculosis and other lung diseases with drug aerosols have been developed. However, all inhalers and nebulizers produce micron-sized drug particles which poorly penetrate into the alveolar region. Recently we have developed a new technology for generation of nanoaerosol particles (NAPs) from biological molecules (antibiotics, proteins) with complete retention of their structural and functional properties. The technology has been tested in treatment of mice infected with pulmonary tularemia. It was found that inhalation of levofloxacin NAPs saved most infected mice if the antibiotic was packed into liposomes before atomization.

In this report the benefits and drawbacks of the new drug form will be discussed. Atomization of a substance into NAPs changes its chemical and physical properties as well as its pharmacodynamics and therapeutic effects. First, unlike the oral application when drug is first subjected to destruction in the stomach and then in the liver inhaled drug quickly penetrate into blood stream and reach other organs without being subjected to proteolysis and hydrolysis. Second, substantial reduction in the working doses is expected in terms of mg/kg, since the drug NAPs are delivered to the infection site and since the number of particles per number of the lung cells may provide a new basis for dosing. It is not excluded, however, that the direct exposure to a highly concentrated drug solution in the area where drug particle landed may produce unusual side effects.

To study potential side effects of nanoaersolized drugs fruit flies (Drosophila melanogaster) were employed as an inexpensive biological model. We showed that exposure of the flies to imidacloprid (IMI) NAPs resulted in their rapid knockdown (T50=88 ± 14 min at 22 °C and T50 = 36± 2 min at 33 °C). It was demonstrated that the concentration dependence of T50 follows the Haber rule, CxT50=const., and that only the IMI NAPs with the diameter below 300 nm contributed to the fly poisoning. Doses inducing knockdown in flies upon oral application were experimentally determined and compared with the doses upon exposure to IMI NAPs. Two models were developed to calculate NAPs doses. First one assumes that IMI NAPs are deposited from all the air volume from which oxygen was consumed. In the second model NAPs deposition is calculated by comparing diffusion of oxygen and NAPs in the fly tracheas. It was found that the tracheal deposition resulting in the knockdown is ~ 1/100 of the oral dose according to the first model and ~ 1/100,000 according to the second model.

Experimental data thus indicate that IMI NAPs quickly penetrate fly nervous cells through the breathing system causing knockdown. Shown here ability of non-volatile insecticide NAPs to be highly effective in killing insects might find applications in the green houses and vegetable storage facilities.