Development and Characterization of Solid Lipid Nanoparticles Loaded with a Highly Active Doxorubicin Derivative.

Barbara Stella,Casimiro Gigliotti,Elena Boggio,Elena Peira,Marina Gallarate,Umberto Dianzani,Chiara Dianzani,Luigi Battaglia,Franco Dosio

doi:10.3390/nano8020110

Abstract

Solid lipid nanoparticles (SLNs) comprise a versatile drug delivery system that has been developed for the treatment of a variety of diseases. The present study will investigate the feasibility of entrapping an active doxorubicin prodrug (a squalenoyl-derivative) in SLNs. The doxorubicin derivative-loaded SLNs are spherically shaped, have a mean diameter of 300–400 nm and show 85% w/w drug entrapment efficiency. The effects on cell growth of loaded SLNs, free doxorubicin and the prodrug have been examined using cytotoxicity and colony-forming assays in both human ovarian cancer line A2780 wild-type and doxorubicin-resistant cells. Further assessments as to the treatment’s ability to induce cell death by apoptosis have been carried out by analyzing annexin-V staining and the activation of caspase-3. The in vitro data demonstrate that the delivery of the squalenoyl-doxorubicin derivative by SLNs increases its cytotoxic activity, as well as its apoptosis effect. This effect was particularly evident in doxorubicin-resistant cells.

Highlights

Anthracycline antitumor antibiotics are amongst the most powerful agents for the treatment of solid malignancies and can boast a wide range of antitumor activity
SLNs are a category of versatile drug delivery systems that have been studied in the biomedical field for several years
The preparation of SLNs using the fatty acid coacervation technique (FACT), which allows the incorporation of drugs in a micellar solution of FA alkaline salts, does not require complex equipment and can be moved for industrial application [27]

Summary

Introduction

Anthracycline antitumor antibiotics are amongst the most powerful agents for the treatment of solid malignancies and can boast a wide range of antitumor activity. Anthracycline therapy is associated with significant general organ toxicity and especially myelosuppression, mucositis and cardiac toxicity [2]. Despite this widespread use of anthracyclines in cancer therapy, their limitations have continued to yield significant amounts of research. The main fields of anthracycline research are the continuing synthesis of novel anthracycline analogues to reverse drug resistance and reduce cardiotoxicity, while improving the delivery of anthracycline drugs is an active field [3]. Doxorubicin-loaded liposomes exhibit efficiencies comparable to those of the conventional anthracycline cytostatic agents, but with less cardiotoxicity. The administration of long-circulating liposomes in clinical practice has been associated with palmar-plantar erythrodysesthesia (“hand-foot” syndrome), which may evolve into ulceration and epidermal necrosis if the chemotherapy cycle is not delayed [6]

Methods

Results

Conclusion