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

Maurizio Viale, Massimiliano Monticone, Irena Maric, Valentina Giglio, Aldo Profumo, Anna Aprile, Michele Cilli, Maria Luisa Abelmoschi, Mattia Rocco

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)760-765
Number of pages6
JournalPharmacological Reports
Volume70
Issue number4
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

Fibrin
Doxorubicin
Gels
Pharmaceutical Preparations
Thrombin
Nanoparticles
Fibrinogen
Ions
Drug Liberation
Biocompatible Materials
Drug Delivery Systems
Tumor Burden
Polymers
Recurrence
Therapeutics

Keywords

  • Doxorubicin
  • Fibrin gels
  • In vitro
  • In vivo
  • Nanoparticles
  • Release kinetics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Characterization of drug release from fibrin gels loaded with different pharmaceutical and experimental doxorubicin formulations. / Viale, Maurizio; Monticone, Massimiliano; Maric, Irena; Giglio, Valentina; Profumo, Aldo; Aprile, Anna; Cilli, Michele; Abelmoschi, Maria Luisa; Rocco, Mattia.

In: Pharmacological Reports, Vol. 70, No. 4, 01.08.2018, p. 760-765.

Research output: Contribution to journalArticle

Viale, Maurizio ; Monticone, Massimiliano ; Maric, Irena ; Giglio, Valentina ; Profumo, Aldo ; Aprile, Anna ; Cilli, Michele ; Abelmoschi, Maria Luisa ; Rocco, Mattia. / Characterization of drug release from fibrin gels loaded with different pharmaceutical and experimental doxorubicin formulations. In: Pharmacological Reports. 2018 ; Vol. 70, No. 4. pp. 760-765.
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AU - Monticone, Massimiliano

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AU - Profumo, Aldo

AU - Aprile, Anna

AU - Cilli, Michele

AU - Abelmoschi, Maria Luisa

AU - Rocco, Mattia

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AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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