Maurizio Viale1, Graziella Vecchio2, Massimiliano Monticone3, Vittorio Bertone4, Valentina Giglio2, Irena Maric3, Michele Cilli5, Vittorio Bocchini6, Aldo Profumo7, Mirco Ponzoni8, Laura Emionite5, Mattia Rocco7. 1. UOC Bioterapie, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genoa, Italy. maurizio.viale@hsanmartino.it. 2. Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy. 3. UOC Bioterapie, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genoa, Italy. 4. Lab. Anatomia Comparata e Citologia, Dipartimento Biologia e Biotecnologie, Università di Pavia "L. Spallanzani", Via Ferrata 9, 27100, Pavia, Italy. 5. UOS Animal Facility, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genoa, Italy. 6. Segreteria Comitato Etico Regione Liguria, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy. 7. UOS Biopolimeri e Proteomica, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genoa, Italy. 8. Laboratorio di Terapie Sperimentali in Oncologia, Istituto G. Gaslini, Via G. Gaslini 5, 16147, Genoa, Italy.
Abstract
PURPOSE: Fibrin gels (FBGs) are potential delivery vehicles for many drugs, and can be easily prepared from purified components. We previously demonstrated their applicability for the release of different doxorubicin (Dox) nanoparticles used clinically or in an experimental stage, such as its inclusion complex with the amino β-cyclodextrin polymer (oCD-NH2/Dox). Here we extend these studies by in vitro and in vivo evaluations. METHODS: An in vitro cytotoxicity model consisting of an overlay of a neuroblastoma (NB) cell-containing agar layer above a drug-loaded FBG layer was used. Local toxicity in vivo (histology and blood analysis) was studied in a mouse orthotopic NB model (SHSY5YLuc+ cells implanted into the left adrenal gland). RESULTS: In vitro data show that FBGs loaded with oCD-NH2/Dox have a slightly lower cytotoxicity against NB cell lines than those loaded with Dox. Fibrinogen (FG), and Ca2+ concentrations may modify this activity. In vivo data support a lower general and local toxicity for FBGs loaded with oCD-NH2/Dox than those loaded with Dox. CONCLUSION: Our results suggest a possible increase of the therapeutic index of Dox when locally administered through FBGs loaded with oCD-NH2/Dox, opening the possibility of using these releasing systems for the treatment of neuroblastoma.
PURPOSE: Fibrin gels (FBGs) are potential delivery vehicles for many drugs, and can be easily prepared from purified components. We previously demonstrated their applicability for the release of different doxorubicin (Dox) nanoparticles used clinically or in an experimental stage, such as its inclusion complex with the amino β-cyclodextrin polymer (oCD-NH2/Dox). Here we extend these studies by in vitro and in vivo evaluations. METHODS: An in vitro cytotoxicity model consisting of an overlay of a neuroblastoma (NB) cell-containing agar layer above a drug-loaded FBG layer was used. Local toxicity in vivo (histology and blood analysis) was studied in a mouse orthotopic NB model (SHSY5YLuc+ cells implanted into the left adrenal gland). RESULTS: In vitro data show that FBGs loaded with oCD-NH2/Dox have a slightly lower cytotoxicity against NB cell lines than those loaded with Dox. Fibrinogen (FG), and Ca2+ concentrations may modify this activity. In vivo data support a lower general and local toxicity for FBGs loaded with oCD-NH2/Dox than those loaded with Dox. CONCLUSION: Our results suggest a possible increase of the therapeutic index of Dox when locally administered through FBGs loaded with oCD-NH2/Dox, opening the possibility of using these releasing systems for the treatment of neuroblastoma.
Entities:
Keywords:
activity in vitro; cyclodextrin polymer; doxorubicin; fibrin gel; toxicity in vivo
Authors: Julie R Park; Rochelle Bagatell; Susan L Cohn; Andrew D Pearson; Judith G Villablanca; Frank Berthold; Susan Burchill; Ariane Boubaker; Kieran McHugh; Jed G Nuchtern; Wendy B London; Nita L Seibel; O Wolf Lindwasser; John M Maris; Penelope Brock; Gudrun Schleiermacher; Ruth Ladenstein; Katherine K Matthay; Dominique Valteau-Couanet Journal: J Clin Oncol Date: 2017-05-04 Impact factor: 44.544
Authors: G Ronald Jenkins; Taewon Lee; Carrie L Moland; Vikrant Vijay; Eugene H Herman; Sherry M Lewis; Kelly J Davis; Levan Muskhelishvili; Susan Kerr; James C Fuscoe; Varsha G Desai Journal: Toxicol Appl Pharmacol Date: 2016-09-17 Impact factor: 4.219
Authors: Pamela Bensimhon; Judith G Villablanca; Leonard S Sender; Katherine K Matthay; Julie R Park; Robert Seeger; Wendy B London; John Stephen F Yap; Susan G Kreissman Journal: Pediatr Blood Cancer Date: 2010-04 Impact factor: 3.167