title: Injectable SN-38-loaded Polymeric Depots for Cancer Chemotherapy of Glioblastoma Multiforme.
abstract: SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo.
  
  
  
  Preparation and characterization of SN-38-loaded depots were performed and evaluated in vitro using human glioblastoma cell line, U-87MG. Antitumor efficacy with different depot administrations including dose, position of depot injection and number of injections were evaluated in tumor model in nude mice.
  
  
  
  Depots encapsulated SN-38 with high encapsulation efficiency (~98.3%). High amount of SN-38 (3.0 ± 0.1 mg) was prolonged and controlled release over time and showed anticancer activity against U-87MG cell line in vitro. For one course administration, depots exhibited better antitumor efficacy and reduced toxicity compared to free SN-38. Elevated doses and multiple injections of SN-38-loaded depots and free SN-38 provided greater tumor growth inhibition and animal survival. All animals received SN-38-loaded depots were well tolerated and survived while most of those received free SN-38 died at day 30. Free SN-38 showed severe toxic effect compared to minimal toxicity from SN-38-loaded depots which was due to lower SN-38 level in systemic circulation. Fluorescence imaging and histopathology confirmed that SN-38 released from depots was detected throughout tumors 35 days post administration.
  
  
  
  SN-38-loaded depots were proved as a promising new treatment for highly invasive glioblastoma multiforme with low acute toxicity due to controlled release of SN-38.
authors: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, 25/25 Puttamonthon 4th Rd., Nakorn Pathom, 73170, Thailand.
authors: Chawan
authors: C
authors: Manaspon
authors: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, 25/25 Puttamonthon 4th Rd., Nakorn Pathom, 73170, Thailand. norased.nas@mahidol.ac.th.
authors: Norased
authors: N
authors: Nasongkla
authors: Academic Services Office, National Laboratory Animal Center, Mahidol University, Nakhorn Pathom, 73170, Thailand.
authors: Khuanjit
authors: K
authors: Chaimongkolnukul
authors: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, 25/25 Puttamonthon 4th Rd., Nakorn Pathom, 73170, Thailand.
authors: Pinunta
authors: P
authors: Nittayacharn
authors: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, 25/25 Puttamonthon 4th Rd., Nakorn Pathom, 73170, Thailand.
authors: Ketpat
authors: K
authors: Vejjasilpa
authors: Academic Services Office, National Laboratory Animal Center, Mahidol University, Nakhorn Pathom, 73170, Thailand.
authors: Kanchana
authors: K
authors: Kengkoom
authors: Department of Surgery, Neurosurgical Unit, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
authors: Atthaporn
authors: A
authors: Boongird
authors: Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
authors: Suradej
authors: S
authors: Hongeng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D064593:Heterografts; D006801:Humans; D007267:Injections; D000077146:Irinotecan; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011091:Polyesters; C000613452:poly(ethylene glycol)-b-poly(lactide-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin
keywords: SN-38; biodegradable polymers; drug delivery system; glioblastoma multiforme; intratumoral injection