Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids
Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids
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DOI：
10.3109/10717544.2014.881633
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发表时间：
2015-08-01
期刊：
影响因子：
6
通讯作者：
Okore, V. C.
中科院分区：
文献类型：
--
作者：
Chinaeke, E. E.;Chime, S. A.;Okore, V. C.
背景：青蒿素及其衍生物被认为是治疗恶性疟疾的基础，因为它们具有高效和快速的作用。目的：制备青蒿琥酯固体脂质微球(SLM)，并对其进行评价。材料与方法：采用差示扫描量热法(DSC)、小角X射线衍射仪(SAXD)、广角X射线衍射仪(WAXD)对其进行表征。采用热熔融均质法制备了自组装膜。对SLM进行了时间依赖的粒径分析、时间依赖的pH稳定性研究、包封率(EE%)和体外药物释放实验。使用伯氏疟原虫感染的小鼠，采用改进的Peter‘s 4天抑制方案进行体内抗疟疾研究。结果和讨论：脂类基质的热谱显示，由于大豆油的加入，Dika蜡的微观结构发生了改变。SAXD和WAXD衍射图表明，脂质基质为非片层状。在pH基本不变的情况下，SLM的粒径随时间的延长而增大。与参照片相比，该固体脂质体片的最大释药效率为80.6%，对青蒿琥酯的缓释效果更好。体内药效学研究表明，与参比片剂相比，青蒿琥酯缓释片对原虫血症有显著的降低作用(p<；0.05)。结论：青蒿琥酯缓释片可每日1次用于疟疾的治疗。
Contexts: Artemisinins and its derivatives are considered the basis in the treatment of Plasmodium falciparum malaria due to their high potency and rapid action. However, they have short half life, low solubility, and poor oral bioavailability, hence the need to formulate sustained release lipid particulate dosage form of these drugs.Objectives: To formulate and evaluate artesunate-loaded solid lipid microparticles (SLMs) based on structured lipid matrices consisting of soybean oil and dika wax.Materials and methods: The lipid matrices were characterized by differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD), and wide-angle X-ray diffraction (WAXD). The SLMs were prepared by hot melt-homogenization. Time-dependent particle size analysis, time-dependent pH stability studies, encapsulation efficiency (EE%), and in vitro drug release were carried out on the SLMs. In vivo anti-malarial studies were performed using a modified Peter's 4-day suppressive protocol using Plasmodium berghei infected mice.Results and discussion: Thermograms of the lipid matrices showed modifications in the microstructure of dika wax as a result of inclusion of soybean oil. SAXD and WAXD diffractograms showed that the lipid matrices were found to be non-lamellar. Particle size of SLM increased with time, while the pH was almost constant. The SLMs had maximum EE% of 80.6% and sustained the release of artesunate more than the reference tablet. In vivo pharmacodynamic studies showed that the SLMs had significant (p < 0.05) reduction in parasitaemia compared with reference tablet.Conclusion: Artesunate-loaded SLMs could be used once daily in the treatment of malaria.