<P><B>Abstract</B></P><P>Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limita...
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https://www.riss.kr/link?id=A107570071
2011
-
SCI,SCIE,SCOPUS
학술저널
482-491(10쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P><B>Abstract</B></P><P>Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limita...
<P><B>Abstract</B></P><P>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<SUB>50</SUB> = 67.2 ng/mL versus Apo2L/TRAIL IC<SUB>50</SUB> = 55.4 ng/mL) with negligible activity loss. Furthermore, <I>in vivo</I> 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</P>