Vasa Dipy M, Bakri Zainab, Donovan Maureen D, O'Donnell Lauren A, Wildfong Peter L D
Division of Pharmaceutical, Administrative, and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, 600 Forbes Ave., Pittsburgh, PA 15282, USA.
Department of Pharmaceutical Science and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 South Grand Ave., Pharmacy Building, Iowa City, IA 52242, USA.
Pharmaceutics. 2021 Jul 23;13(8):1126. doi: 10.3390/pharmaceutics13081126.
Ribavirin is a water-soluble antiviral compound which, owing to its inability to cross the blood-brain barrier, has limited effectiveness in treating viruses affecting the central nervous system. Direct nose-to-brain delivery was investigated for ribavirin in combination with poloxamer 188, an excipient known to enhance the absorption of drug compounds administered intranasally. Composite solid microparticles suitable for intranasal insufflation were prepared by suspending fine crystals of ribavirin in a matrix of poloxamer 188, which were cryogenically milled and characterized to ensure that ribavirin remained stable throughout preparation. In vitro diffusion of ribavirin across a semi-permeable regenerated cellulose membrane showed comparable cumulative drug release after 180 min from both fine solid particles (<20 µm) and 1:1 ribavirin:poloxamer microparticles (d = 20 µm); however, the initial release from polymer microparticles was slower, owing to gel formation on the membrane surface. When solid ribavirin was directly deposited on excised olfactory mucosa, either as fine drug particles or 1:1 ribavirin:poloxamer microparticles, permeation was significantly increased from microparticles containing poloxamer 188, suggesting additional interactions between the polymer and olfactory mucosa. These data indicate that for highly water-soluble drugs such as ribavirin or drugs subject to efflux by the nasal mucosa, a formulation of poloxmer-containing microparticles can enhance permeability across the olfactory epithelium and may improve direct nose-to-brain transport.
利巴韦林是一种水溶性抗病毒化合物，由于其无法穿过血脑屏障，在治疗影响中枢神经系统的病毒方面效果有限。研究了利巴韦林与泊洛沙姆188联合使用的直接鼻至脑给药方式，泊洛沙姆188是一种已知可增强鼻内给药药物化合物吸收的辅料。通过将利巴韦林细晶体悬浮在泊洛沙姆188基质中制备适用于鼻内吹入的复合固体微粒，对其进行低温研磨和表征以确保利巴韦林在整个制备过程中保持稳定。利巴韦林在体外通过半透性再生纤维素膜的扩散显示，在180分钟后，细固体颗粒（<20 µm）和1:1利巴韦林：泊洛沙姆微粒（d = 20 µm）的累积药物释放相当；然而，由于膜表面形成凝胶，聚合物微粒的初始释放较慢。当固体利巴韦林以细药物颗粒或1:1利巴韦林：泊洛沙姆微粒的形式直接沉积在切除的嗅粘膜上时，含有泊洛沙姆188的微粒的渗透显著增加，这表明聚合物与嗅粘膜之间存在额外的相互作用。这些数据表明，对于像利巴韦林这样的高水溶性药物或易被鼻粘膜外排的药物，含泊洛沙姆微粒的制剂可以增强跨嗅上皮的通透性，并可能改善直接鼻至脑的转运。
