Probing adsorption of DSPE-PEG2000 and DSPE-PEG5000 to the surface of felodipine and griseofulvin nanocrystals

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• 作者：Hanna A. Rydberg ; Marianna Yanez Arteta ; Staffan Berg ; Lennart Lindfors ; Kalle Sigfridsson ; ^{carl-gustav.sigfridsson@astrazeneca.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Poorly water-soluble drug ; Nanoparticle stabilization ; Drug formulation ; Wet-milling ; Quartz crystal microbalance with dissipation monitoring ; PEGylated lipids
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 August 2016
• 年：2016
• 卷：510
• 期：1
• 页码：232-239
• 全文大小：1343 K

文摘

Nanosized formulations of poorly water-soluble drugs show great potential due to improved bioavailability. In order to retain colloidal stability, the nanocrystals need to be stabilized. Here we explore the use of the poly(ethylene glycol) (PEG) conjugated phospholipids DSPE-PEG2000 and DSPE-PEG5000 as stabilizers of felodipine and griseofulvin nanocrystals. Nanocrystal stability and physicochemical properties were examined and the interaction between the PEGylated lipids and the nanocrystal surface as well as a macroscopic model surface was investigated. Using quartz crystal microbalance with dissipation monitoring both mass adsorption and the thickness of the adsorbed layer were estimated. The results indicate that the PEGylated lipids are adsorbed as flat layers of around 1–3 nm, and that DSPE-PEG5000 forms a thicker layer compared with DSPE-PEG2000. In addition, the mass adsorption to the drug crystals and the model surface are seemingly comparable. Furthermore, both DSPE-PEG2000 and DSPE-PEG5000 rendered stable drug nanocrystals, with a somewhat higher surface binding and stability seen for DSPE-PEG2000. These results suggest DSPE-PEG2000 and DSPE-PEG5000 as efficient nanocrystal stabilizers, with DSPE-PEG2000 giving a somewhat higher surface coverage and superior colloidal stability, whereas DSPE-PEG5000 shows a more extended structure that may have advantages for prolongation of circulation time in vivo and facilitation for targeting modifications.