Development and in-vitro evaluation of controlled release drug-loaded polymeric nanoparticles from dry powder inhaler formulation

We investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs. NPs were prepared using a straightforward co-assembly reaction carried out by the intermolecular hydrogen bonding among PEtOx, tannic acid (TA), and CIP. The prepared NPs were characterised by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The CIP was determined by validated HPLC and UV spectrophotometry methods.

The CIP loading into the PEtOx was between 21–67% and increased loading was observed with the increasing concentration of CIP. The NP sizes of PEtOx with or without drug loading were between 196–350 nm and increased with increasing drug loading. The in vitro CIP release showed the maximum cumulative release of about 78% in 168 h with a burst release of 50% in the first 12 h. The kinetics of CIP release from NPs followed non-Fickian or anomalous transport thus suggesting the drug release was regulated by both diffusion and polymer degradation. The in vitro aerosolisation study carried out using a Twin Stage Impinger (TSI) at 60 L/min air flow showed the fine particle fraction (FPF) between 34.4% and 40.8%. The FPF was increased with increased drug loading. The outcome of this study revealed the potential of the polymer PEtOx as a carrier for developing CIP-loaded PEtOx NPs as DPI formulation for pulmonary delivery against LRTIs.

本研究探讨了以干粉吸入剂（DPI）配方形式，利用聚（2-乙基-2-恶唑啉）（PEtOx）纳米颗粒（NPs）装载环丙沙星（CIP）的制备及其在治疗下呼吸道感染（LRTIs）中的潜在肺递送。NPs的制备采用了一种简便的共组装反应，该反应由PEtOx、单宁酸（TA）和CIP之间的分子间氢键作用实现。制备的NPs通过扫描电子显微镜（SEM）、动态光散射（DLS）、傅里叶变换红外光谱（FTIR）、粉末X射线衍射分析（PXRD）、差示扫描量热法（DSC）和热重分析（TGA）进行了表征。CIP的含量通过验证的高效液相色谱（HPLC）和紫外分光光度法确定。PEtOx中的CIP负载量介于21%至67%之间，随着CIP浓度的增加，负载量也随之提高。PEtOx纳米颗粒的大小（含药或不含药）在196至350纳米之间，并随着药物负载量的增加而增大。体外CIP释放实验显示，在168小时内累积释放量最大可达78%，前12小时释放量占50%。CIP从NPs中的释放动力学遵循非菲克（Fickian）或异常传输，这表明药物释放受扩散和聚合物降解的共同调节。采用双级冲击器（TSI）在60 L/min的空气流量下进行的体外气雾化研究表明，细颗粒物分数（FPF）介于34.4%至40.8%之间，随着药物负载量的增加，FPF也随之提高。本研究结果表明，聚合物PEtOx作为CIP负载PEtOx NPs的载体，在开发用于肺递送治疗LRTIs的DPI配方方面具有潜在价值。