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Preparation and characterization of Apo2L/TNF-related apoptosis-inducing ligand-loaded human serum albumin nanoparticles with improved stability and tumor distribution.
- Source :
-
Journal of Pharmaceutical Sciences . Feb2011, Vol. 100 Issue 2, p482-491. 10p. - Publication Year :
- 2011
-
Abstract
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limitations, which include a weak pharmacokinetic profile, namely, a short biological half-life and rapid renal clearance, and an inability to form a homotrimeric structure. In this research, we attempted to develop a sustained release nanoparticle (NP) formulation that stabilizes Apo2L/TRAIL and preserves its antitumor activity. Apo2L/TRAIL-loaded human serum albumin (HSA) NPs were prepared using a desolvation technique optimized by particle size, zeta-potential, and entrapment efficiency. Apo2L/TRAIL in HSA-NPs continuously released over 24 h at 37°C in phosphate buffered saline and rat plasma condition, and the biological activity of Apo2L/TRAIL-HSA-NPs was preserved (IC = 67.2 ng/mL versus Apo2L/TRAIL IC = 55.4 ng/mL) with negligible activity loss. Furthermore, in vivo pharmacokinetic profiles and tumor distribution demonstrated the superiority of Apo2L/TRAIL-HSA-NPs over Apo2L/TRAIL. The circulating half-life period was significantly prolonged from 9.8 to 90.7 min (9.2-fold enhancement), and drug bioavailability was clearly enhanced on the basis of area under the curve analysis (2.7-fold). And tumor distribution of Apo2L/TRAIL-HSA-NPs was also increased at 1 h after injection, which was about 14-fold (1-h point) over that of Apo2L/TRAIL. These results show that Apo2L/TRAIL-loaded HSA-NPs should be considered as potential long-acting cancer agents. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:482-491, 2011 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223549
- Volume :
- 100
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 56630175
- Full Text :
- https://doi.org/10.1002/jps.22298