Anti-inflammatory effect from indomethacin nanoparticles inhaled by male mice.
The respiratory system provides entry for drug nanoparticles to cure systemic diseases. The modern devices that are available on the market of therapeutic aerosol delivery systems have a number of disadvantages. There remains a need for an alternative means that is low cost, convenient, and capable of producing small-sized particles. On the other hand, one-third of the modern drugs are poorly water soluble. Many currently available injectable formulations of such drugs can cause side effects that originate from detergents and other agents used for their solubilization. The aerosol lung administration may by a good way for delivery of the water-insoluble drugs. We present here a new way for the generation of drug nanoparticles suitable for many water insoluble substances based on the evaporation-condensation route. In this paper the indomethacin nanoaerosol formation was studied and its anti-inflammatory effect to the outbred male mice was examined. The evaporation-condensation aerosol generator consisted of a horizontal cylindrical quartz tube with an outer heater. Argon flow was supplied to the inlet and the aerosol was formed at the outlet. The particle mean diameter and number concentration were varied in the ranges 3 to 200 nm and 10(3) to 10(7) cm(-3), respectively. The liquid chromatography and X-ray diffraction methods have shown the nanoparticles consist of the amorphous phase indomethacin. The aerosol lung administration experiments were carried out in the whole-body exposure chamber. Both the lung deposited dose and the particle deposition efficiency were determined as a function of the mean particle diameter for mice being housed into the nose-only exposure chambers. The anti-inflammatory action and side pulmonary effects caused by the inhalation of indomethacin nanoparticles were investigated. It was found that the aerosol administration was much more effective than the peroral treatment. The aerosol route required a therapeutic dose six orders of magnitude less than that for peroral administration.
Onischuk
Andrei A
AA
Institute of Chemical Kinetics & Combustion, RAS, Novosibirsk, 630090, Russia. onischuk@kinetics.nsc.ru
Tolstikova
Tatjana G
TG
Sorokina
Irina V
IV
Zhukova
Natalja A
NA
Baklanov
Anatoly M
AM
Karasev
Vladimir V
VV
Dultseva
Galina G
GG
Boldyrev
Vladimir V
VV
Fomin
Vasilii M
VM
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D053758:Nanoparticles; D011654:Pulmonary Edema / Q000139:chemically induced; D014961:X-Ray Diffraction
D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin