Journal
MOLECULAR PHARMACEUTICS
Volume 10, Issue 5, Pages 2031-2044Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp400054e
Keywords
thiolated type B gelatin nanoparticles; poly(ethylene glycol); epidermal growth factor receptor (EGFR) targeting; long circulation time; passive tumor targeting; active tumor targeting; biodistribution; targeting efficiency; pharmacokinetics; two compartment model; population analysis
Funding
- National Cancer Institute's Alliance in Nanotechnology for Cancer's Center for Cancer Nanotechnology Excellence (CCNE) [U54-CA151881]
- NIH [EB-002027]
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The objective of this study was to evaluate qualitative and quantitative biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated type B gelatin nanoparticles in vivo in subcutaneous human pancreatic adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted nanoparticles showed preferential and sustained accumulation in the tumor mass, especially at early time points. Higher blood concentrations and higher tumor accumulations were observed with PEG-modified and EGFR-targeted nanoparticles during the study (AUC(last): 17.38 and 19.56%ID/mL.h in blood, 187 and 322%ID/g.h in tumor for PEG-modified and EGFR-targeted nanoparticles, respectively), as compared to control, unmodified particles (AUC(last): 10.71%ID/mL.h in blood and 138%ID/g.h in tumor). EGFR-targeted nanoparticles displayed almost twice tumor targeting efficiency than either PEG modified or the unmodified nanoparticles, highlighting the efficacy of the active targeting strategy. In conclusion, this study shows that EGFR-targeted and PEG modified nanoparticles were suitable vehicles for specific systemic delivery in subcutaneous Panc-1 tumor xenograft models.
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