کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485563 | 1114360 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Preparation and Characterization of Apo2L/TNF-Related Apoptosis-Inducing Ligand-Loaded Human Serum Albumin Nanoparticles with Improved Stability and Tumor Distribution
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Preparation and Characterization of Apo2L/TNF-Related Apoptosis-Inducing Ligand-Loaded Human Serum Albumin Nanoparticles with Improved Stability and Tumor Distribution Preparation and Characterization of Apo2L/TNF-Related Apoptosis-Inducing Ligand-Loaded Human Serum Albumin Nanoparticles with Improved Stability and Tumor Distribution](/preview/png/2485563.png)
چکیده انگلیسی
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 (IC50 = 67.2 ng/mL versus Apo2L/TRAIL IC50 = 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 2, February 2011, Pages 482-491
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 2, February 2011, Pages 482-491
نویسندگان
Tae Hyung Kim, Hai-Hua Jiang, Yu Seok Youn, Chan Woong Park, Sung Mook Lim, Cheng-Hao Jin, Kyung Kook Tak, Hye Suk Lee, Kang Choon Lee,