title: Prolonged local retention of subcutaneously injected polymers monitored by noninvasive SPECT imaging.
abstract: Polymers are widely applied to drug delivery systems because polymers are generally excreted from the body more slowly than small molecules. Subcutaneous injection is one plausible means of administration. In this study, the in vivo behaviors of subcutaneously injected polymers, linear poly(glutamic acid) (Poly-Glu), acetylated dendrimer (Ac-den) and collagen peptide-conjugated dendrimer (CP-den), were investigated. Single photon emission computed tomography (SPECT) imaging was used to noninvasively monitor the in vivo behaviors. Diethylenetriaminepentaacetic acid (DTPA) was conjugated to these polymers, which were labeled with radioactive (111)In. These (111)In-DTPA-bearing polymers (Poly-Glu-DTPA, Ac-den-DTPA and CP-den-DTPA) and unconjugated DTPA were subcutaneously injected into tumor-bearing mice, which were subjected to SPECT imaging. These (111)In-DTPA-bearing polymers were largely retained at the injection site for at least 1 day, whereas the unconjugated DTPA was rapidly cleared from the whole body through excretion. Poly-Glu-DTPA and Ac-den-DTPA were partly accumulated in the kidney (and the liver), but the CP-den-DTPA was not. However, these (111)In-DTPA-bearing polymers were accumulated in the liver and the kidney following intravenous administration. These results indicate that the subcutaneously injected polymers did not largely gain substantial access to the systemic circulation, which is useful for a depot of drug around the injection site.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: kojima@chem.osakafu-u.ac.jp.
authors.forename: Chie
authors.initials: C
authors.lastname: Kojima
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Niki
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
mesh_terms: D000107:Acetylation; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D003094:Collagen / Q000737:chemistry; D003692:Delayed-Action Preparations; D050091:Dendrimers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D004369:Pentetic Acid / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011099:Polyglutamic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D003692:Delayed-Action Preparations; D050091:Dendrimers; D010455:Peptides; D011108:Polymers; D011099:Polyglutamic Acid; D004369:Pentetic Acid; D003094:Collagen
keywords: Dendrimer; Poly(glutamic acid); Polymer; SPECT imaging; Subcutaneous injection