Composition-dependent structural changes and antitumor activity of ASC-DP/DSPE-PEG nanoparticles

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• 作者：Kenjirou Higashi^a ; Fusako Mibu^a ; Kengo Saito^b ; Waree Limwikrant^c ; Keiji Yamamoto^a ; Kunikazu Moribe^a ; ^{moribe@faculty.chiba-u.jp}
• 关键词：Nanoparticles ; Ascorbyl 2 ; 6-dipalmitate ; DSPE-PEG ; Disk ; Tube ; Cytotoxicity
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：99
• 期：Complete
• 页码：24-31
• 全文大小：1180 K
• 卷排序：99

文摘

Ascorbyl 2,6-dipalmitate (ASC-DP) and distearoyl phosphatidylethanolamine polyethylene glycol 2000 (DSPE-PEG) formed stable nanoparticles at a molar ratio of less than or equal to 2:1 after dispersing the solvent-evaporated film in water. The mean particle sizes measured by dynamic light scattering were within the range of ca. 100–160 nm. Composition-dependent changes of the ASC-DP and DSPE-PEG molecular states within the film were analyzed by wide-angle X-ray diffraction and infrared (IR) and solid-state nuclear magnetic resonance (NMR) spectroscopy. Transmission electron microscopy (TEM) of nanoparticles revealed that ASC-DP/DSPE-PEG changed from a micelle to a disk and tubular structure as the molar ratio increased. Quantitative solution-state 1H NMR measurements elucidated the structure of nanoparticle in water; the core could be composed of ASC-DP and hydrophobic acyl chains of DSPE, whereas the hydrophilic PEG chains of DSPE-PEG on the surface form the hydration shell to stabilize the nanoparticle dispersion in water. Cytotoxicity of ASC-DP against cancer cell lines was observed by using ASC-DP/DSPE-PEG nanoparticles, and no cytotoxicity against normal cells was found. Thus, the ASC-DP/DSPE-PEG formulation, with tumor cell specific cytotoxicity, can be applicable for cancer monotherapy or in combination with other anticancer drugs.