Characterization of drug release from fibrin gels loaded with different pharmaceutical and experimental doxorubicin formulations

• Published in: Pharmacological reports 2018-08, Vol.70 (4), p.760-765
• Main Authors: Viale, Maurizio, Monticone, Massimiliano, Maric, Irena, Giglio, Valentina, Profumo, Aldo, Aprile, Anna, Cilli, Michele, Abelmoschi, Maria Luisa, Rocco, Mattia
• Format: Article
• Language: English
• Subjects: Animals; Calcium - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - analysis; Doxorubicin - pharmacokinetics; Drug Compounding; Drug Delivery Systems; Drug Implants - administration & dosage; Drug Implants - pharmacokinetics; Drug Liberation - drug effects; Drug Safety and Pharmacovigilance; Female; Fibrin - administration & dosage; Fibrin - chemistry; Fibrin gels; Gels - chemistry; Humans; In vitro; In vivo; Injections, Subcutaneous; Mice; Nanoparticles; Nanoparticles - chemistry; Original Article; Pharmacotherapy; Pharmacy; Release kinetics; Thrombin - pharmacology; Time Factors; Tumor Stem Cell Assay
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2018.02.014

•Fibrin gels (FBGs) are good vehicles for anticancer drug local delivery.•We studied the release of some doxorubicin-charged nanoparticles loaded in FBGs.•Factors involved in FBG gelation have effects that depend on drug formulation. Local delivery of anticancer drugs represents a desirable type of treatment. Nevertheless, characteristics such as availability, biocompatibility, ease of operation, and efficacy sometimes represent difficult to overcome hurdles. Fibrin gels (FBGs) may be attractive biomaterials for local treatment when loaded with different chemotherapeutics or with polymer-anticancer-drug conjugates and nanoparticles. These components, linked together, might represent candidates to counteract local recurrences or reduce the volume of inoperable tumors. In the present study we analyzed the features of in vitro release of different formulations of doxorubicin (DOXO) from FBGs, and in vivo FBGs degradation. In vitro DOXO release from FBGs was studied as a function of thrombin and Ca2+ ion concentrations. DOXO was loaded in FBGs either alone or pre-incorporated in nanoparticles characterized by different physical features. The FBGs in vivo degradation was analyzed after sc or ip positioning. Our results suggest that each of the factors involved in the FBGs preparation may have different effects on drug release. In particular, the fibrinogen (FG) concentration and, above all, the DOXO formulation were found to have the greatest impact. Not surprisingly, we have also found a longer permanence in vivo of FBGs prepared at the highest thrombin, Ca2+ ion, and FG concentrations. The aim of this work was to study the effect of several conditions for preparing drug delivery systems based on FBGs loaded with different clinical or experimental formulations of DOXO. Our data identify some of these modalities that will be tested in vivo to evaluate their antitumor activity.