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

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• 作者：Sun Young Min^a ; Hyeong Jun Byeon^a ; Changkyu Lee^a ; Jisoo Seo^a ; Eun Seong Lee^b ; Beom Soo Shin^c ; Han-Gon Choi^d ; Kang Choon Lee^a ; Yu Seok Youn^a ; ^{ysyoun@skku.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Albumin ; Nanoparticles ; TRAIL ; Paclitaxel ; Pancreatic cancer ; Anti-cancer agent
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：494
• 期：1
• 页码：506-515
• 全文大小：3600 K

文摘

Nanoparticle albumin-bound (nab™) 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 ∼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 ∼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 mm³ and 0.18 g vs. 1126.8 mm³ 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.