title: Composition-dependent structural changes and antitumor activity of ASC-DP/DSPE-PEG nanoparticles.
abstract: 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-state1H 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Mibu
authors.affiliation: Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Saito
authors.affiliation: Faculty of Pharmacy, Mahidol University, 447 Sri Ayudhya Road, Ratchatewi, Bangkok 10400, Thailand.
authors.forename: Waree
authors.initials: W
authors.lastname: Limwikrant
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: moribe@faculty.chiba-u.jp.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010168:Palmitates / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010168:Palmitates; D010714:Phosphatidylethanolamines; C549095:ascorbyl 2,6-dipalmitate; D014867:Water; D011092:Polyethylene Glycols; D001205:Ascorbic Acid
keywords: Ascorbyl 2,6-dipalmitate; Cytotoxicity; DSPE-PEG; Disk; Nanoparticles; Tube