- 作者：Shaheen Sultana ; Rashid Ali ; Sushama Talegaonkar ; Farhan Jalees Ahmad ; Gaurav Mittal ; Aseem Bhatnagar
- 关键词：Alendronate sodium ; Technetium-99m ; Biodistribution ; Gamma scintigraphy ; Sub-acute inhalation toxicity ; Histopathology
- 刊名：Environmental Toxicology and Pharmacology
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：36
- 期：2
- 页码：636-647
- 全文大小：1904 K
Introduction
Alendronate sodium is a bisphosphonate agent used for the treatment of osteoporosis and other bone diseases. It has a strong chelating property to bind or, to some extent, counteract the effects of substances, such as magnesium, calcium citrate, ferrous fumarate, carbonyl iron, as well as the zinc gluconate, sulfate and acetate salts. The objective of the present study was to evaluate lung deposition and sub-acute inhalation toxicity of the alendronate sodium respiratory formulation.Methods
Particle dimension of aerosols of alendronate was measured using a particle size analyzer. Alendronate was radiolabeled using Technetium-99m for in vitro and in vivo biodistribution studies. Alendronate at doses, 0.5 % , 1.0 % , and 1.5 % in ethanol-saline respiratory formulation was inhaled twice a day up to 5 weeks for inhalation toxicity investigations. Hematological, biochemical and lung toxicity biomarkers in bronchoalveolar lavage (BAL) fluid were determined at the end of the experiment. Histopathological analysis of lung tissues was carried out to observe any microscopic changes
Results
Particle size analysis revealed the size within 300-500 nm. Anderson cascade impactor results showed that the particles exhibited higher respirable fraction (55.52 % ) with MMAD of 4.66 ¦Ìm. Hematology, serum biochemistry and lung toxicity biomarkers in BAL fluid performed in the sub-acute toxicity studies indicated no adverse effects of alendronate sodium inhalation except for a significant increase in cholesterol levels and marginal increase in BAL fluid protein. At autopsy, no histopathological changes in major organs were observed.
Conclusions
The lung deposition and safety evaluation data observed from these studies suggested that aerosolized nanosized alendronate sodium by the inhalation route could be a new and promising route of administration as an antidote to radioactive substances through an increase in the bioavailability of the drug as well as a decrease in side effects on systemic delivery.