title: Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles.
abstract: To improve the in vivo tumor targeting characteristics of polymeric nanoparticles, three glycol chitosan (GC-20 kDa, GC-100 kDa, and GC-250 kDa) derivatives with different molecular weights were modified with cholanic acid at the same molar ratio. The resulting amphiphilic glycol chitosan-cholanic acid conjugates self-assembled to form glycol chitosan nanoparticles (GC-20 kDa-NP, GC-100 kDa-NP, and GC-250 kDa-NP) under aqueous conditions. The physicochemical properties of all three glycol chitosan nanoparticles, including degree of substitution with cholanic acid, surface charge, particle size and in vitro stability, were similar regardless of molecular weight. In vivo tissue distribution, time-dependent excretion, and tumor accumulation of glycol chitosan nanoparticles labeled with the near-infrared (NIR) fluorophore, Cy5.5, were monitored in SCC7 tumor-bearing mice, using NIR fluorescence imaging systems. Glycol chitosan nanoparticles displayed prolonged blood circulation time, decreased time-dependent excretion from the body, and elevated tumor accumulation with increasing polymer molecular weight. The results collectively suggest that high molecular weight glycol chitosan nanoparticles remain for longer periods in the blood circulation, leading to increased accumulation at the tumor site. Accordingly, we propose that enhanced tumor targeting by high molecular weight glycol chitosan nanoparticles is related to better in vivo stability, based on a pharmacokinetic improvement in blood circulation time.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Yun Sik
authors.initials: YS
authors.lastname: Nam
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Hae Yun
authors.initials: HY
authors.lastname: Nam
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics; D002793:Cholic Acids / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D002793:Cholic Acids; D004337:Drug Carriers; D011108:Polymers; C118638:glycol-chitosan; D048271:Chitosan; C007036:cholanic acid