Goldie Kaul1, Mansoor Amiji. 1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, MA 02115, USA.
Abstract
PURPOSE: In order to develop a safe and effective systemically-administered biodegradable nanoparticle delivery system for solid tumors, the comparative biodistribution profiles of gelatin and poly(ethylene-glycol)(PEG)-modified (PEGylated) gelatin nanoparticles was examined in subcutaneous Lewis lung carcinoma (LLC)-bearing female C57BL/6J mice. METHODS: Type-B gelatin and PEGylated gelatin nanoparticles were radiolabeled ((125)I) for the in vivo biodistribution studies after intravenous (i.v.) administration through the tail vein in LLC-bearing mice. At various time intervals, the mice were sacrificed and blood, tumor, and major organs harvested for analysis of radioactivity corresponding to the localization of the nanoparticles. Percent recovered dose was determined and normalized to the weight of the fluid or tissue sample. Non-compartmental pharmacokinetic analysis was performed to determine the long-circulating property and preferential tumor targeting potential of PEGylated gelatin nanoparticles in vivo. RESULTS: From the radioactivity in plasma and various organs collected, it was evident that the majority of PEGylated nanoparticles were present either in the blood pool or taken up by the tumor mass and liver. For instance, after 3 h, the concentrations of PEGylated gelatin nanoparticles was almost 2-fold higher in the blood pool than the control gelatin nanoparticles. PEGylated gelatin nanoparticles remained in the blood pool for a longer period of time due to the steric repulsion effect of the PEG chains as compared to the gelatin nanoparticles. In addition, approximately 4-5% of the recovered dose of PEGylated gelatin nanoparticles was present in the tumor mass for up to 12 h. The plasma and the tumor half-lives, the mean residence time, and the area-under-the-curve of the PEGylated gelatin nanoparticles were significantly higher than those for the gelatin nanoparticles. CONCLUSIONS: The results of this study show that PEGylated gelatin nanoparticles do possess long circulating properties and can preferentially distribute in the tumor mass after systemic delivery.
PURPOSE: In order to develop a safe and effective systemically-administered biodegradable nanoparticle delivery system for solid tumors, the comparative biodistribution profiles of gelatin and poly(ethylene-glycol)(PEG)-modified (PEGylated) gelatin nanoparticles was examined in subcutaneous Lewis lung carcinoma (LLC)-bearing female C57BL/6J mice. METHODS: Type-B gelatin and PEGylated gelatin nanoparticles were radiolabeled ((125)I) for the in vivo biodistribution studies after intravenous (i.v.) administration through the tail vein in LLC-bearing mice. At various time intervals, the mice were sacrificed and blood, tumor, and major organs harvested for analysis of radioactivity corresponding to the localization of the nanoparticles. Percent recovered dose was determined and normalized to the weight of the fluid or tissue sample. Non-compartmental pharmacokinetic analysis was performed to determine the long-circulating property and preferential tumor targeting potential of PEGylated gelatin nanoparticles in vivo. RESULTS: From the radioactivity in plasma and various organs collected, it was evident that the majority of PEGylated nanoparticles were present either in the blood pool or taken up by the tumor mass and liver. For instance, after 3 h, the concentrations of PEGylated gelatin nanoparticles was almost 2-fold higher in the blood pool than the control gelatin nanoparticles. PEGylated gelatin nanoparticles remained in the blood pool for a longer period of time due to the steric repulsion effect of the PEG chains as compared to the gelatin nanoparticles. In addition, approximately 4-5% of the recovered dose of PEGylated gelatin nanoparticles was present in the tumor mass for up to 12 h. The plasma and the tumor half-lives, the mean residence time, and the area-under-the-curve of the PEGylated gelatin nanoparticles were significantly higher than those for the gelatin nanoparticles. CONCLUSIONS: The results of this study show that PEGylated gelatin nanoparticles do possess long circulating properties and can preferentially distribute in the tumor mass after systemic delivery.
Authors: H Q Mao; K Roy; V L Troung-Le; K A Janes; K Y Lin; Y Wang; J T August; K W Leong Journal: J Control Release Date: 2001-02-23 Impact factor: 9.776
Authors: Zhi Yang; Jeffrey Leon; Mike Martin; John W Harder; Rui Zhang; Dong Liang; Wei Lu; Mei Tian; Juri G Gelovani; Alex Qiao; Chun Li Journal: Nanotechnology Date: 2009-03-31 Impact factor: 3.874