Comparing the Inhalable and Parenteral Forms of Erythropoietin in Enhancement of Reticulocytes Count



Varshosaz J¹ ; Minaiyan M² ; Sami M³ Show Affiliations
Source: Journal of Isfahan Medical School Published:2014

Abstract

Background: In patients with renal failure, frequent use of erythropoietin is necessary for long times due to serious anemia. The aim of the present study was production of an inhalable dry powder of erythropoietin and comparison it with its parenteral form in erythrocytes count enhancement. Methods: The inhalable powder was prepared using spray-drying of the mixture of poly (methyl-vinyl ether-maleic anhydride), 2-hydroxy propyl-alpha-cyclodextrin and terhalose. The freeze-dried aqueous solution of erythropoietin was mixed with the spray-dried powder in 1:4 ratio. The particle size and drug content uniformity were determined in the final dried powder. There were 3 groups of rats each containing 6 animals. One group received 840 IU as subcutaneous (sc) injection of regular solution of the drug. The other was treated with blank pulmonary powder and the last group with 840 IU of the spray dried pulmonary powder. Six days before starting the treatment, all animals were fed with 1 % (w/w) ferrous sulfate as gavage. Blood sampling was carried out from eye retro-orbital vein at 0, 1, 4 and 7 days after treatment and the reticulocytes were counted by hemocytometer. Findings: There was not any significant difference between control, inhalable and parenteral groups at days of 0 and 1 after administration. At the day 4, there was significant difference between all three groups and reticulocytes count was higher in the inhalable group than the parenteral (P < 0.001) and the control groups (P < 0.010). At the 7th day, the results were similar to the 4th day but the reticulocytes count of ininhalable group was significantly higher than the control and parenteral groups (P < 0.001 for both). Conclusion: The spray-dried inhalable powder of erythropoietin was more effective than subcutaneous injection form in enhancing the reticulocytes count for a longer time and may be a good replacement for the parenteral form of this drug.