Rehydrated Lyophilized Rifampicin-Loaded mPEG-DSPE Formulations for Nebulization
Rehydrated Lyophilized Rifampicin-Loaded mPEG-DSPE Formulations for Nebulization
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DOI：
10.1208/s12249-010-9428-6
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Darwis, Yusrida
中科院分区：
文献类型：
--
作者：
Abdulla, Juma Masoud Abdulla;Tan, Yvonne Tze-Fung;Darwis, Yusrida
使用两种不同分子量的聚-（环氧乙烷）-嵌段-二硬脂酰磷脂酰-乙醇胺（mPEG 2000-DSPE和mPEG 5000-DSPE）聚合物制备负载利福平的纳米粒。所研究的所有制剂的粒度在162-395 nm的范围内。包封率（EE）不受共聚物的分子量，并获得最高的EE（100%），药物与共聚物的比例为1：5。差示扫描量热法（DSC）的热分析图显示，利福平负载的PEG-DSPE纳米粒子的Tg转移到一个较低的值，表明在聚合物基质中的利福平包封。傅立叶变换红外光谱显示药物和两种共聚物之间没有化学相互作用。体外药物释放超过3天，并遵循一级释放动力学和Higuchi扩散模型。再水化的冻干利福平mPEG-DSPE制剂的雾化具有2.6 μ m的质量中值空气动力学直径和42%的细颗粒分数。共聚物的分子量不影响制剂的空气动力学特性。因此，这两种mPEG-DSPE是作为利福平肺部递送载体的有希望的候选者。
Rifampicin-loaded nanoparticles were prepared using two different molecular weights of poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG2000-DSPE and mPEG5000-DSPE) polymers. Particle sizes of all formulations studied were in the range of 162-395 nm. The entrapment efficiency (EE) was not affected by the copolymer's molecular weight, and the highest EE (100%) was obtained with drug to copolymer ratio of 1:5. The differential scanning calorimetry (DSC) thermograms showed Tg of rifampicin-loaded PEG-DSPE nanoparticles that shifted to a lower value, indicating entrapment of rifampicin in polymer matrix. The Fourier transformed infrared spectra revealed no chemical interactions between the drug and both copolymers. The in vitro drug release from the formulations occurred over 3 days and followed first-order release kinetic and Higuchi diffusion model. The nebulization of rehydrated lyophilized rifampicin mPEG-DSPE formulations had mass median aerodynamic diameter of 2.6 A mu m and fine particle fraction of 42%. The aerodynamic characteristic of the preparations was not influenced by the molecular weight of the copolymers. Therefore, it is suggested that both mPEG-DSPE are promising candidates as rifampicin carrier for pulmonary delivery.