Control of in vivo blood clearance time of polymeric micelle by stereochemistry of amphiphilic polydepsipeptides

• Published in: Journal of controlled release 2012-08, Vol.161 (3), p.821-825
• Main Authors: Makino, Akira, Hara, Eri, Hara, Isao, Yamahara, Ryo, Kurihara, Kensuke, Ozeki, Eiichi, Yamamoto, Fumihiko, Kimura, Shunsaku
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; blood; blood flow; Cell Line; Depsipeptides - administration & dosage; Depsipeptides - blood; Depsipeptides - chemistry; fluorescence; Fluorescent Dyes - administration & dosage; Fluorescent Dyes - analysis; Fluorescent Dyes - chemistry; General pharmacology; Humans; hydrophilicity; hydrophobicity; image analysis; Indocyanine Green - administration & dosage; Indocyanine Green - analysis; Indocyanine Green - chemistry; lactic acid; Lactic Acid - administration & dosage; Lactic Acid - blood; Lactic Acid - chemistry; Lactosome; Medical sciences; Mice; Mice, Nude; Micelles; Molecular imaging; Neoplasms - metabolism; Peptides - administration & dosage; Peptides - blood; Peptides - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(lactic acid); Poly(sarcosine); Polyesters; Polymeric micelle; Polymers - administration & dosage; Polymers - chemistry; Sarcosine - administration & dosage; Sarcosine - analogs & derivatives; Sarcosine - blood; Sarcosine - chemistry; stereochemistry; Stereocomplex; Stereoisomerism
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.05.006

Polymeric micelle, “Lactosome,” is composed of amphiphilic polydepsipeptide with a hydrophobic block of helical poly(l-lactic acid) (PLLA) and a hydrophilic block of poly(sarcosine). Lactosome was labeled by incorporation of poly(lactic acid) having a near-infrared fluorescence (NIRF) chromophore, and studied on blood clearance and tumor imaging. In vivo blood clearance time of Lactosome was prolonged with incorporation of poly(d-lactic acid) (PDLA), but decreased with poly(d,l-lactic acid) (PDLLA). NIRF imaging with applying these Lactosomes to tumor-bearing mice revealed that the tumor/background intensity ratio increased with incorporation of PDLLA. Stereochemistry in the hydrophobic core of self-assemblies is thus an important factor for determining physical stability in the blood stream and consequently contrast in imaging. [Display omitted]