Yousfan Amal, Al Khatib Arwa Omar, Salman Afrah M H, Abu Elella Mahmoud H, Barrett Glyn, Michael Nicholas, Zariwala Mohammed Gulrez, Al-Obaidi Hisham
School of Pharmacy, University of Reading, Reading RG6 6AD, U.K.
Faculty of Pharmacy, Al Ahliyya Amman University, Amman 19111, Jordan.
Mol Pharm. 2025 Jan 6;22(1):113-130. doi: 10.1021/acs.molpharmaceut.4c00594. Epub 2024 Oct 8.
This study aims to develop an innovative microencapsulation method for coated Polymyxin B, utilizing various polysaccharides such as hydroxypropyl β-cyclodextrin, alginate, and chitosan, implemented through a three-fluid nozzle (3FN) spray drying process. High-performance liquid chromatography (HPLC) analysis revealed that formulations with a high ratio of sugar cage, hydroxypropyl β-cyclodextrin (HPβCD), and sodium alginate (coded as ALGCDP) resulted in a notable 16-fold increase in Polymyxin B recovery compared to chitosan microparticles. Morphological assessments using fluorescence labeling confirmed successful microparticle formation with core/shell structures. Alginate-based formulations exhibited distinct layers, while chitosan formulations showed uniform fluorescence throughout the microparticles. Focused beam reflectance and histograms from fluorescence microscopic measurements provided insights into physical size analysis, indicating consistent sizes of 6.8 ± 1.2 μm. Fourier-transform infrared (FTIR) spectra unveiled hydrogen bonding between Polymyxin B and other components within the microparticle structures. The drug release study showed sodium alginate's sustained release capability, reaching 26 ± 3% compared to 94 ± 3% from the free solution at the 24 h time point. Furthermore, the antimicrobial properties of the prepared microparticles against two Gram-negative bacteria, and , were investigated. The influence of various key excipients on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values was evaluated. Results demonstrated effective bactericidal effects of ALGCDP against both and . Additionally, the antibiofilm assay highlighted the potential efficacy of ALGCDP against the biofilm viability of and , with concentrations ranging from 3.9 to 500 μg/m. This signifies a significant advancement in antimicrobial drug delivery systems, promising improved precision and efficacy in combating bacterial infections.
本研究旨在开发一种用于包衣多粘菌素B的创新微囊化方法，利用各种多糖，如羟丙基-β-环糊精、海藻酸盐和壳聚糖，通过三流体喷嘴（3FN）喷雾干燥工艺实现。高效液相色谱（HPLC）分析表明，与壳聚糖微粒相比，糖笼、羟丙基-β-环糊精（HPβCD）和海藻酸钠比例高的制剂（编码为ALGCDP）使多粘菌素B的回收率显著提高了16倍。使用荧光标记的形态学评估证实成功形成了具有核/壳结构的微粒。基于海藻酸盐的制剂呈现出明显的层状结构，而壳聚糖制剂在整个微粒中显示出均匀的荧光。聚焦光束反射率和荧光显微镜测量的直方图为物理尺寸分析提供了见解，表明尺寸一致，为6.8±1.2μm。傅里叶变换红外（FTIR）光谱揭示了多粘菌素B与微粒结构内其他成分之间的氢键。药物释放研究表明海藻酸钠具有持续释放能力，在24小时时间点达到26±3%，而游离溶液为94±3%。此外，还研究了制备的微粒对两种革兰氏阴性菌的抗菌性能。评估了各种关键辅料对最低抑菌浓度（MIC）和最低杀菌浓度（MBC）值的影响。结果表明ALGCDP对两种菌均具有有效的杀菌作用。此外，抗生物膜试验突出了ALGCDP对两种菌生物膜活力的潜在疗效，浓度范围为3.9至500μg/m。这标志着抗菌药物递送系统取得了重大进展，有望在对抗细菌感染方面提高精度和疗效。
