Optimization of Acoustic Liposomes for Improved In Vitro and In Vivo Stability
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Liposomes encapsulating perfluoropropane gas, termed acoustic liposomes (ALs), which can serve both for ultrasound (US) imaging and US-mediated gene delivery, have been reported. However, the echogenicity of ALs decreases within minutes in vivo due to gas diffusion and leakage, hindering time-consuming procedures such as contrast-enhanced 3D US imaging and raising the need for improvement of their stability.
The stability of ALs preparations incorporating increasing ratios of anionic / unsaturated phospholipids, polyethylene glycol (PEG)ylated phospholipid and cholesterol was investigated by measurement of their reflectivity over time using a high-frequency US imaging system, both in vitro and in vivo.
The retention of echogenicity of ALs in vitro is enhanced with increasing molar ratios of PEGylated lipids. Addition of 10 molar percent of an anionic phospholipid resulted in a 31% longer half-life, while cholesterol had the opposite effect. Assessment of the stability of an optimized composition showed a more than 2-fold increase of the detection half-life in mice.
Presence of a PEG coating not only serves to provide “stealth” properties in vivo, but also contributes to the retention of the encapsulated gas. The optimized ALs reported here can be used as a contrast agent for lengthier imaging procedures.
KEY WORDScontrast agent drug delivery gas encapsulation microbubbles polyethylene glycol ultrasound
Acknowledgments AND DISCLOSURES
We are sincerely grateful to Rui Chen, Sachiko Horie, Yukiko Watanabe (Department of Biomedical Engineering, Tohoku University) and Li Li (Department of Radiology, Tohoku University Graduate School of Medicine) for providing technical advice on in vivo ultrasound imaging. We thank Shiro Mori for providing us with MXH-10/Mo/lpr/lpr mice, and Thirumala Govender for her invaluable help and knowledge regarding nanoparticles and polymers. T. Kodama received a Grant-in-Aid for Scientific Research (B) (23300183) and the Grant-in-Aid for challenging exploratory research (24650286).
- 1.Kodama T, Tomita N, Yagishita Y, Horie S, Funamoto K, Hayase T, et al. Volumetric and angiogenic evaluation of antitumor effects with acoustic liposome and high-frequency ultrasound. Cancer Res. 2011.Google Scholar
- 14.Negishi Y, Tsunoda Y, Endo-Takahashi Y, Oda Y, Suzuki R, Maruyama K, et al. Local gene delivery system by bubble liposomes and ultrasound exposure into joint synovium. J Drug Deliv. 2011;2011.Google Scholar
- 15.Ikeda-Dantsuji Y, Feril LB, Tachibana K, Ogawa K, Endo H, Harada Y, et al. Synergistic effect of ultrasound and antibiotics against Chlamydia trachomatis-infected human epithelial cells in vitro. Ultrason Sonochem. 2010.Google Scholar