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

• Published in: European journal of pharmaceutical sciences 2017-03, Vol.99, p.24-31
• Main Authors: Higashi, Kenjirou, Mibu, Fusako, Saito, Kengo, Limwikrant, Waree, Yamamoto, Keiji, Moribe, Kunikazu
• Format: Article
• Language: English
• Subjects: A549 Cells; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Ascorbic Acid - chemistry; Ascorbyl 2,6-dipalmitate; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; Cytotoxicity; Disk; Drug Carriers - chemistry; Drug Stability; DSPE-PEG; Humans; Hydrophobic and Hydrophilic Interactions; Magnetic Resonance Spectroscopy - methods; Micelles; Nanoparticles; Nanoparticles - chemistry; Palmitates - chemistry; Particle Size; Phosphatidylethanolamines - chemistry; Polyethylene Glycols - chemistry; Tube; Water - chemistry; X-Ray Diffraction - methods
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2016.11.029

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. 100–160nm. 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. [Display omitted]