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Preparation of amifostine polylactide-co-glycolide microspheres and its irradiation protective to mouse through oral
Ting-Li Lu1, Wei-guang Sun, Wen Zhao
1Key Laboratory for Space Biosciences & Biotechnology, Faculty of Life Science, Northwestern Polytechnical University, Xi'an, China. lutinglixinxin@nwpu.edu.cn
Abstract:
The objectives of this study were to prepare the amifostine polylactide-co-glycolide (PLGA) microsphere and investigate its irradiation protective to mouse through oral administration. Amifostine-loaded PLGA microsphere was formulated using a modified double emulsion-solvent evaporation technique. The microsphere particle was spherical with a mean diameter of 2.8 ± 0.1 μm. Release data of amifostine PLGA microsphere was tested in phosphate-buffered saline at 37°C using a dialysis method and its release profiles was biphasic, showing a relatively large burst effect (50%) over the first 6 h, followed by a slower release phase, which sustained with 80% amifostine released in 48 h and almost 100% release till 6 days (144 h). A diffusion-controlled release model (Higuchi equation, R² = 0.9725) was obtained for amifostine releasing from PLGA microsphere. The radiation experiment was performed by applied cobalt-60 γ-radiation source. One hour before γ-radiation exposure, the mouse was orally given free amifostine and PLGA microsphere, respectively. The irradiation effects, such as blood cell concentration, superoxidase dismutase (SOD) activity and malondialdehyde (MDA) level were monitored. The results indicated that amifostine PLGA microsphere was more irradiation protective to mouse than that of free amifostine under the same oral administration route.
Insights
This study developed amifostine-loaded polylactide-co-glycolide (PLGA) microspheres for oral administration. The amifostine PLGA microspheres demonstrated superior radioprotective effects in mice compared to free amifostine.
Area of Science:
- Biomedical Engineering
- Radiopharmacology
- Drug Delivery Systems
Background:
- Amifostine is a radioprotective agent.
- Developing effective oral delivery systems for amifostine is crucial for radiation protection.
- Polylactide-co-glycolide (PLGA) microspheres offer potential for sustained drug release.
Purpose of the Study:
- To prepare amifostine-loaded PLGA microspheres.
- To evaluate the in vitro release characteristics of amifostine from PLGA microspheres.
- To investigate the in vivo radioprotective efficacy of oral amifostine PLGA microspheres in mice.
Main Methods:
- Amifostine-loaded PLGA microspheres were formulated using a modified double emulsion-solvent evaporation technique.
- In vitro drug release was assessed using a dialysis method in phosphate-buffered saline at 37°C.
- In vivo radioprotection was evaluated in mice exposed to cobalt-60 gamma radiation, monitoring blood cell counts, SOD activity, and MDA levels.
Main Results:
- The PLGA microspheres were spherical with a mean diameter of 2.8 ± 0.1 μm.
- Amifostine release exhibited a biphasic profile: a 50% burst effect in 6 hours, followed by sustained release (80% in 48 hours, ~100% in 144 hours).
- Amifostine PLGA microspheres showed significantly better radioprotective effects than free amifostine in mice.
Conclusions:
- Amifostine-loaded PLGA microspheres can be effectively prepared using the described method.
- The PLGA microspheres provide sustained release of amifostine, suitable for oral administration.
- Oral administration of amifostine PLGA microspheres offers enhanced radioprotection in mice compared to free amifostine.
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