title: In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein.
abstract: The key to making a practicable hydrogel for pharmaceutical or medical purposes is to endow it with relevant properties, i.e., facile fabrication, gelation time-controllability, and in situ injectability given a firm basis for safety/biocompatibility. Here, the authors describe an in situ gelling, injectable, albumin-cross-linked polyethylene glycol (PEG) hydrogel that was produced using a thiol-maleimide reaction. This hydrogel consists of two biocompatible components, namely, thiolated human serum albumin and 4-arm PEG20k-maleimide, and can be easily fabricated and gelled in situ within 60s by simply mixing its two components. In addition, the gelation time of this system is controllable in the range 15s to 5min. This hydrogel hardly interacted with an apoptotic TRAIL protein, ensuring suitable release profiles that maximize therapeutic efficacy. Specifically, tumors (volume: 278.8mm(3)) in Mia Paca-2 cell-xenografted BALB/c nu/nu mice treated with the TRAIL-loaded HSA-PEG hydrogel were markedly smaller than mice treated with the hydrogel prepared via an amine-N-hydroxysuccinimide reaction or non-treated mice (1275.5mm(3) and 1816.5mm(3), respectively). We believe that this hydrogel would be a new prototype of locally injectable sustained-release type anti-cancer agents, and furthermore offers practical convenience for a doctor and universal applicability for a variety of therapeutic proteins.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Insoo
authors.initials: I
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Ji Su
authors.initials: JS
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Byeon
authors.affiliation: 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.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 330 Geumrak 1-ri, Hayang Eup, Gyeongsan si, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 426-791, Republic of Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea. Electronic address: ysyoun@skku.edu.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D020100:Hydrogels; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols; D012709:Serum Albumin / Q000737:chemistry; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D012709:Serum Albumin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D011092:Polyethylene Glycols
keywords: Albumin; Hydrogel; In situ formation; Pancreatic cancer; Polyethylene glycol; TNF-related apoptosis-inducing ligand