Biodistribution and pharmacokinetic analysis of long-circulating thiolated gelatin nanoparticles following systemic administration in breast cancer-bearing mice.
The objective of the present study was to modify thiolated gelatin nanoparticles with poly(ethylene glycol) (PEG) chains and examine their long circulating and tumor-targeting properties in vivo in an orthotopic a human breast adenocarcinoma xenograft model. The crosslinked nanoparticle systems were characterized to have a size of 150-250 nm with rapid payload release properties in a highly reducing environment. Upon PEG modification, the nanoparticle size increased to 300-350 nm in diameter. The presence of PEG chains on the surface was confirmed by characterization with electron spectroscopy for chemical analysis. The in vivo long-circulating potential, biodistribution and passive tumor targeting of the controls, and PEG-modified thiolated gelatin nanoparticles were evaluated by injecting indium-111 (111In)-labeled nanoparticles into breast tumor (MDA-MB-435)-bearing nude mice. Upon modification with PEG, the nanoparticles were found to have longer circulation times, with the plasma and tumor half-lives of 15.3 and 37.8 h, respectively. The results also showed preferential localization of thiolated nanoparticles in the tumor mass. The resulting nanoparticulate systems with long circulation properties could be used to target encapsulated drugs and genes to tumors passively by utilizing the enhanced permeability and retention effect of the tumor vasculature.
Kommareddy
Sushma
S
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, MA 02115, USA.
Amiji
Mansoor
M
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D005260:Female; D005780:Gelatin / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009368:Neoplasm Transplantation; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D013499:Surface Properties; D014018:Tissue Distribution
D007205:Indium Radioisotopes; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D005780:Gelatin