Studies On Lung-targeting Gelatin Microspheres Of Erythromycin

Erythromycin is widely used in humans to control bacterial diseases, such as aerobic gram-positive and-negative cocci, anaerobes, legionella bacteria, chlamydia and mycoplasma. Antibacterial spectrum of erythromycin was similar to penicillin and erythromycin was the preferred drug of treatment of mycoplasma pneumonia, legionella pneumonia. But erythromycin has a short effective treatment time (t1/2=1.4-2h) and distributes all over the body, which is likely to cause untoward effects. If the antibiotics drug is micronized into microspheres with suitable particle size, it can be addressed directly to the lung by the mechanical interception of capillary bed in the lungs, and improve pulmonary drug concentration to maximize their effectiveness against disease and minimize the adverse side effects. In the present study, erythromycin gelatin microspheres have been prepared and investigated in order to predict their potential as targeted delivery system for the intravenous drug administration, which would be lung-targeting with low distribution in other tissues, and would increase curative effect and reduce the side-effects.EM-GMS were prepared by the method of emulsion. By using single-factor test and orthogonal test, preparation technology was optimized. The surface morphology of EM-GMS showed spherical shape with smooth and porous surface. The average drug loading efficiency,the average encapsulation efficiency and the average yield of EM-GMS were 13.56 %,55.82% and 69.12%, respectively. The arithmetic mean diameter of the microspheres was 15.62μm with over 90% of the microspheres ranging from 7.00 to 28.00μm. The DSC curve of EM-GMS confirmed that EM was loaded within the microspheres.In vitro release of EM-GMS was carried out by using phosphate buffer (pH7.4, 0.1M) as release medium. The amount of erythromycin was determined by UV spectrophotometry and the cumulate release was calculated.The in vitro release profile of the microspheres could be described by a biexponential equation Q/100=0.8047-0.17exp(?128.9t)-0.6347exp (?1.378t).To evaluate the safety of the lung targeting erythromycin gelatin microspheres,some experiments were conducted,including acute toxicity test, hemolysis test in vitro, and vein irritation test.In the rabbit vein irritation test, no irritation was observed. Hemolysis tests showed no hemolysis on erythrocyte of rabbit.The LD50 was found to be of 173.07, 191.01, 337.70 mg/kg for EM-GMS, GMS, and EA, respectively. The results showed some toxicity come from the mechanical trapping effect of the microspheres in the pulmonary capillary vessel. In the rabbit vein irritation test, no irritation or sensitization reactions were observed. Hemolysis test showed no hemolysis on erythrocyte of rabbit.In vivo experiment of EM-GMS, the high performance liquid chromatography with UV detector was utilized for the determination of erythromycin contention in rabbit tissues, The lung targeting effect was evaluated by drug targeting index (DTI).The erythromycin concentration in lung tissue was higher than that in liver, kidney, spleen and heart, and 5.45 times than that of EA in lung tissue. DTI in lung was found to be 3.38 and 6.65 on administration of EM-GMS after 0.25 and 2 h, respectively. The lung targeting effect was proved remarkable.