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Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer

Title
Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer
Author
최한곤
Keywords
Albumin; Nanoparticles; TRAIL; Paclitaxel; Pancreatic cancer; Anti-cancer agent; APOPTOSIS-INDUCING LIGAND; IMPROVED ANTITUMOR-ACTIVITY; DRUG-DELIVERY SYSTEMS; LUNG-CANCER; IN-VIVO; TUMOR; PROTEIN; CELLS; APO2L/TRAIL; CHALLENGES
Issue Date
2015-10
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v. 494, No. 1, Page. 506-515
Abstract
Nanoparticle albumin-bound (nab (TM)) technology is an effective way of delivering hydrophobic chemotherapeutics. We developed a one-pot/one-step formulation of paclitaxel (PTX)-bound albumin nanoparticles with embedded tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/PTX HSA-NP) for the treatment of pancreatic cancer. TRAIL/PTX HSA-NPs were fabricated using a high-pressure homogenizer at a TRAIL feeding ratio of 0.2%, 1.0%, and 2.0%. TRAIL/PTX HSA-NPs were spherical and became larger in size (170-230 nm) with increasing TRAIL amount (0.2-2.0%). The loading efficiencies of PTX were in the range of similar to 86.4% and significantly low at 2.0% TRAIL (60.4%). Specifically, the inhibitory concentrations (IC50) of TRAIL (1.0 or 2.0%)/PTX HSA-NPs were ˃20-fold lower than that of plain PTX-HSA NP (0.032 +/- 0.06, 0.022 +/- 0.005, and 0.96 +/- 0.15 ng/ml, respectively) in pancreatic Mia Paca-2 cells. Considering TRAIL loading, bioactivity, and particle size, TRAIL(1.0%)/PTX HSA-NPs were determined as the optimal candidate for further studies. TRAIL(1.0%)/PTX HSA-NPs displayed substantially greater apoptotic activity than plain PTX HSA-NP in both FACS and TUNEL analysis. The loaded PTX and TRAIL were gradually released from the TRAIL(1.0%)/PTX HSA-NPs until similar to 24 h, which is considered to be a sufficient time for delivery to the tumor tissue. TRAIL(1.0%)/PTX HSA-NP displayed markedly more antitumor efficacy than plain PTX HSA-NP in Mia Paca-2 cell-xenografted mice in terms of tumor volume (size) and weight (213.9 mm(3) and 0.18 g vs. 1126.8 mm(3) and 0.80 g, respectively). These improved in vitro and in vivo performances were due to the combined synergistic effects of PTX and TRAIL. We believe that this TRAIL/PTX HSA-NP would have potential as a novel apoptosis-based anticancer agent. (C) 2015 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0378517315301538http://hdl.handle.net/20.500.11754/39299
ISSN
0378-5173; 1873-3476
DOI
10.1016/j.ijpharm.2015.08.055
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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