Fibrin Gels Entrapment of a Poly-Cyclodextrin Nanocarrier as a Doxorubicin Delivery System in an Orthotopic Model of Neuroblastoma: Evaluation of In Vitro Activity and In Vivo Toxicity

• Published in: Pharmaceutical research Vol. 36; no. 8; pp. 115 - 12
• Main Authors: Viale, Maurizio, Vecchio, Graziella, Monticone, Massimiliano, Bertone, Vittorio, Giglio, Valentina, Maric, Irena, Cilli, Michele, Bocchini, Vittorio, Profumo, Aldo, Ponzoni, Mirco, Emionite, Laura, Rocco, Mattia
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2019; Springer; Springer Nature B.V
• Subjects: Adrenal glands; Analysis; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood; Calcium; Calcium ions; Cell Line, Tumor; Cell lines; Cell Proliferation - drug effects; Cell Survival - drug effects; Cellulose - chemistry; Cyclodextrins; Cyclodextrins - chemistry; Cytotoxicity; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - blood; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Carriers - toxicity; Drug delivery; Entrapment; Female; Fibrin; Fibrin - chemistry; Fibrinogen; Gels; Health aspects; Heterografts; Histology; Humans; Medical examination; Medical Law; Mice, Nude; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - toxicity; Neuroblastoma; Neuroblastoma - drug therapy; Pharmacology/Toxicology; Pharmacy; Research Paper; β-Cyclodextrin; toxicity; doxorubicin; activity; cyclodextrin polymer; fibrin gel; activity in vitro; toxicity in vivo
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-019-2636-1

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-NH 2 /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-NH 2 /Dox have a slightly lower cytotoxicity against NB cell lines than those loaded with Dox. Fibrinogen (FG), and Ca 2+ concentrations may modify this activity. In vivo data support a lower general and local toxicity for FBGs loaded with oCD-NH 2 /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-NH 2 /Dox, opening the possibility of using these releasing systems for the treatment of neuroblastoma.