title: Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer.
abstract: 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 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.
authors: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors: Sun Young
authors: SY
authors: Min
authors: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors: Hyeong Jun
authors: HJ
authors: Byeon
authors: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors: Changkyu
authors: C
authors: Lee
authors: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors: Jisoo
authors: J
authors: Seo
authors: Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors: Eun Seong
authors: ES
authors: Lee
authors: College of Pharmacy, Catholic University of Daegu, 330 Geumrak 1-ri, Hayang Eup, Gyeongsan si, Gyeongbuk 712-702, Republic of Korea.
authors: Beom Soo
authors: BS
authors: Shin
authors: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Republic of Korea.
authors: Han-Gon
authors: HG
authors: Choi
authors: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors: Kang Choon
authors: KC
authors: Lee
authors: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea. Electronic address: ysyoun@skku.edu.
authors: Yu Seok
authors: YS
authors: Youn
mesh_terms: D000418:Albumins / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D020128:Inhibitory Concentration 50; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D004337:Drug Carriers; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D017239:Paclitaxel
keywords: Albumin; Anti-cancer agent; Nanoparticles; Paclitaxel; Pancreatic cancer; TRAIL