Organic Solution Advanced Spray-Dried Microparticulate/Nanoparticulate Dry Powders of Lactomorphin for Respiratory Delivery: Physicochemical Characterization, In Vitro Aerosol Dispersion, and Cellular Studies.
Organic Solution Advanced Spray-Dried Microparticulate/Nanoparticulate Dry Powders of Lactomorphin for Respiratory Delivery: Physicochemical Characterization, In Vitro Aerosol Dispersion, and Cellular Studies.
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DOI：
10.3390/pharmaceutics13010026
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发表时间：
2020-12-25
期刊：
影响因子：
5.4
通讯作者：
Mansour HM
中科院分区：
文献类型：
--
作者：
Alabsi W;Al-Obeidi FA;Polt R;Mansour HM
本研究的目的是将Lactomorphin （MMP2200）制备成纯喷雾干燥（SD）粉末，并与赋形剂海藻糖共喷雾干燥（co-SD）粉末；使用干粉吸入器（DPI）进行鼻内和肺深部给药。乳啡肽是一种糖肽，是为控制中度至重度疼痛而开发的。采用先进的密闭喷雾干燥颗粒工程技术，从稀有机溶液中合理设计和生产颗粒。采用不同的分析技术进行了全面的物理化学表征，分析了颗粒大小、颗粒形态、颗粒表面形态、固态转变、结晶度/非结晶度和残余含水量。利用衰减全反射-傅里叶变换红外（ATR-FTIR）确定了颗粒的化学成分，并用共聚焦拉曼显微镜（CRM）确定了颗粒的化学均匀性。通过分析和计算方法测定了乳酸tomorphin的溶解度和分配系数（LogP），揭示了乳酸tomorphin的亲水性。通过将固态Lactomorphin样品暴露在高温（62°C）和零相对湿度（RH）下，以及高温（62°C）和高相对湿度（75%）下，进行热降解研究，以评估这两种不同条件下Lactomorphin的稳定性。固体处理过的颗粒通过fda批准的人体DPI装置到达下气道，表现出优异的气溶胶分散性能。细胞活力reazurin实验表明，Lactomorphin对鼻上皮细胞、肺细胞、内皮细胞和星形胶质细胞均安全，可达1000 μg/mL。
The purpose of this study was to formulate Lactomorphin (MMP2200) in its pure state as spray-dried(SD) powders, and with the excipient Trehalose as co-spray-dried(co-SD) powders; for intranasal and deep lung administration with Dry Powder Inhalers (DPI). Lactomorphin is a glycopeptide which was developed for the control of moderate to severe pain. Particles were rationally designed and produced by advanced spray drying particle engineering in a closed mode from a dilute organic solution. Comprehensive physicochemical characterization using different analytical techniques was carried out to analyze the particle size, particle morphology, particle surface morphology, solid-state transitions, crystallinity/non-crystallinity, and residual water content. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR), and Confocal Raman Microscopy (CRM) confirmed the particles’ chemical homogeneity. The solubility and Partition coefficient (LogP) of Lactomorphin were determined by the analytical and computational methodology and revealed the hydrophilicity of Lactomorphin. A thermal degradation study was performed by exposing samples of solid-state Lactomorphin to a high temperature (62 °C) combined with zero relative humidity (RH) and to a high temperature (62 °C) combined with a high RH (75%) to evaluate the stability of Lactomorphin under these two different conditions. The solid-state processed particles exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device to reach lower airways. The cell viability resazurin assay showed that Lactomorphin is safe up to 1000 μg/mL on nasal epithelium cells, lung cells, endothelial, and astrocyte brain cells.
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影响因子：
8
作者：
Duan, Jinghua;Vogt, Frederick G.;Mansour, Heidi M.
通讯作者：
Mansour, Heidi M.
影响因子：
--
作者：
Currier, Glenn;Walsh, Patrick
通讯作者：
Walsh, Patrick
影响因子：
9.8
作者：
Alexander-Williams, JM;Rowbotham, DJ
通讯作者：
Rowbotham, DJ
影响因子：
8.8
作者：
Blessy M;Patel RD;Prajapati PN;Agrawal YK
通讯作者：
Agrawal YK
DOI：
10.1124/jpet.104.069393
发表时间：
2004-10-01
影响因子：
3.5
作者：
Elmagbari, NO;Egleton, RD;Bilsky, EJ
通讯作者：
Bilsky, EJ