ABSTRACT
For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 5 x 10(3) metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was started and continued for 12 days. Thalidomide was orally administrated 30 mg/kg/day and glucantime was administrated intraperitoneally (200 mg/kg/day). It was shown that the combined therapy is more effective than single therapies with each one of the drugs since the foot pad swelling in the group of mice received thalidomide and glucantime was significantly decreased (0.9 +/- 0.2 mm) compared to mice treated with either glucantime, thalidomide, or carrier alone (1.2 +/- 0.25, 1.4 +/- 0.3, and 1.7 +/- 0.27 mm, respectively). Cytokine study showed that the effect of thalidomide was not dependent on IL-12; however, it up-regulated IFN-gamma and down-regulated IL-10 production. Conclusively, thalidomide seems promising as a conjunctive therapy with antimony in murine model of visceral leishmaniasis.
Subject(s)
Mice , Female , Animals , Time Factors , Thalidomide/pharmacology , Organometallic Compounds/pharmacology , Mice, Inbred BALB C , Meglumine/pharmacology , Leishmaniasis, Visceral/drug therapy , Leishmania major/drug effects , Interleukin-12/analysis , Interleukin-10/analysis , Interferon-gamma/analysis , Immunosuppressive Agents/pharmacology , Drug Therapy, Combination , Disease Progression , Disease Models, Animal , Cells, Cultured , Antiprotozoal Agents/pharmacologyABSTRACT
Dry powder inhalers [DPIs] have attained considerable attention due to their propellant-free formulations and the patient's inherent coordination with actuation. Generally, DPI formulations consist of a micronized drug alone or mixed with carrier particles. This study was carried out to investigate the effects of carrier particle size and weight fraction on aerosolisation behaviour of cromolyn sodium [CS]. Pharmatose[R] 450M and Pharmatose[R] 325M, two commercial alpha -lactose monohydrate with different particle sizes, were blended in two different fractions [30 and 50% w/w] with CS. A low resistance device [Spinhaler[R]] and a medium resistance device [Cyclohaler[R]], were used to evaluate the effect of inhaler design on the deposition profiles of CS. The in vitro deposition of the formulations was determined using a twin stage impinger [TSI]. Fine particle dose, fine particle fraction and emitted dose of the drug were depended to both formulation and inhalation devices. Fine particle fractions of the drug aerosolised from the formulations ranged from 9.35 up to 36.45%. The highest fine particle fraction was produced by formulation containing 50% Pharmatose[R] 450M as carrier. Cyclohaler[R] showed higher efficiency in aerosolisation of CS compared to Spinhaler[R]