title: PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy.
abstract: The aim of the current study was to investigate the antitumor potential of poly (D,L-lactic-co-glycolic acid) microspheres (PLGA MSs) containing polyethylene glycol (PEG)-conjugated (PEGylated) tumor necrosis factor-related apoptosis-inducing ligand (PEG-TRAIL). PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 μm in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively). The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer.
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Hyeong Jun
authors: HJ
authors: Byeon
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Insoo
authors: I
authors: Kim
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Ji Su
authors: JS
authors: Choi
authors: Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of Korea.
authors: Eun Seong
authors: ES
authors: Lee
authors: Department of Pharmacy, College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Republic of Korea.
authors: Beom Soo
authors: BS
authors: Shin
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Yu Seok
authors: YS
authors: Youn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C552093:PEGylated tumor necrosis factor-related apoptosis-inducing ligand; D011993:Recombinant Fusion Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols
keywords: L-lactic-co-glycolic acid); PEGylation; Poly(D; TRAIL; controlled release; pancreatic cancer
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