title: A sulfate polysaccharide/TNF-related apoptosis-inducing ligand (TRAIL) complex for the long-term delivery of TRAIL in poly(lactic-co-glycolic acid) (PLGA) microspheres.
abstract: OBJECTIVE
  The aim was to develop a long-term delivery system for Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) without chemical modification (such as pegylation).
  
  
  METHODS
  A nanocomplex system between the positively charged TRAIL and the negatively charged chondroitin sulfate (CS) (CS/TRAIL) was designed and applied in poly(lactide-co-glycolide) (PLGA) microspheres (MSs).
  
  
  RESULTS
  A nanocomplex of approximately 200 nm was easily formed in a weight ratio of 2 TRAIL to CS (TC2) at pH 5.0. The cytotoxicity of CS/TRAIL against HeLa cells was similar to that of native TRAIL. The complex also had higher loading efficiency (above 95%) in PLGA MSs prepared by the multi-emulsion method than that of native TRAIL. The release behaviour of TRAIL from the PLGA MSs was monitored. Although the release of TRAIL from native TRAIL-loaded PLGA MSs (TMS0) was almost complete after 3 days, TC2-loaded PLGA MSs (TMS2) showed sustained TRAIL release without an initial burst for 10 days. The released TRAIL from TMS2 led to cytotoxicity accompanied by massive apoptosis of cancer cells. TMS2 significantly inhibited tumour growth in an in-vivo xenograft model in mice, without any loss of body weight after treatment.
  
  
  CONCLUSIONS
  From the results, we concluded that TC-loaded PLGA MSs have the potential for long-term delivery of TRAIL without side effects.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Gyeonggi-do College of Pharmacy, SungKyunKwan University, Suwon City, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.forename: Dooyong
authors.initials: D
authors.lastname: Jeong
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Kang
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D004355:Drug Stability; D005260:Female; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002809:Chondroitin Sulfates