title: Antitumor efficacy and intratumoral distribution of SN-38 from polymeric depots in brain tumor model.
abstract: We investigate antitumor efficacy and 2D and 3D intratumoral distribution of 7-ethyl-10-hydroxycamptothecin (SN-38) from polymeric depots inside U-87MG xenograft tumor model in nude mice. Results showed that polymeric depots could be used to administer and controlled release of a large amount of SN-38 directly to the brain tumor model. SN-38 released from depots suppressed tumor growth, where the extent of suppression greatly depended on doses and the number of depot injections. Tumor suppression of SN-38 from depots was three-fold higher in animals which received double injections of depots at high dose (9.7 mg of SN-38) compared to single injection (2.2 mg). H&E staining of tumor sections showed that the area of tumor cell death/survival of the former group was two-fold higher than those of the latter group. Fluorescence imaging based on self-fluorescent property of SN-38 was used to evaluate the intratumoral distribution of this drug compared to histological results. The linear correlation between fluorescence intensity and the amount of SN-38 allowed quantitative determination of SN-38 in tumor tissues. Results clearly showed direct correlation between the amount of SN-38 in tumor sections and cancer cell death. Moreover, 3D reconstruction representing the distribution of SN-38 in tumors was obtained. Results from this study suggest the rationale for intratumoral drug administration and release of drugs inside tumor, which is necessary to design drug delivery systems with efficient antitumor activity.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakorn Pathom 73170, Thailand.
authors.forename: Ketpat
authors.initials: K
authors.lastname: Vejjasilpa
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakorn Pathom 73170, Thailand norased.nas@mahidol.ac.th.
authors.forename: Norased
authors.initials: N
authors.lastname: Nasongkla
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakorn Pathom 73170, Thailand.
authors.forename: Chawan
authors.initials: C
authors.lastname: Manaspon
authors.affiliation: Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Noppadol
authors.initials: N
authors.lastname: Larbcharoensub
authors.affiliation: Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Atthaporn
authors.initials: A
authors.lastname: Boongird
authors.affiliation: Department of Paediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Nipan
authors.initials: N
authors.lastname: Israsena
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D000077146:Irinotecan; D002166:Camptothecin
keywords: Biodegradable polymer; SN-38; brain tumor model; drug delivery system; intratumoral