Functionalized Diterpene Parvifloron D-loaded Hybrid Nanoparticles for Targeted Delivery in Melanoma Therapy

Abstract

Aim: Parvifloron D is a natural diterpene with a broad and not selective cytotoxicity toward human tumor cells. In order to develop a targeted antimelanoma drug delivery platform for Parvifloron D, hybrid nanoparticles were prepared with biopolymers and functionalized with α-melanocyte stimulating hormone. Results/methodology: Nanoparticles were produced according to a solvent displacement method and the physicochemical properties were assessed. It was shown that Parvifloron D is cytotoxic and can induce, both as free and as encapsulated drug, cell death in melanoma cells (human A375 and mouse B16V5). Parvifloron D-loaded nanoparticles showed a high encapsulation efficiency (87%) and a sustained release profile. In vitro experiments showed the nanoparticles’ uptake and cell internalization. Conclusion: Hybrid nanoparticles appear to be a promising platform for long-term drug release, presenting the desired structure and a robust performance for targeted anticancer therapy.

Keywords:

• α-melanocyte-stimulating hormone
• cutaneous melanoma
• hybrid nanoparticles
• parvifloron D
• sustained release
• targeted delivery

Acknowledgements

The authors would like to thank P Cavaco, É Viegas and F Falcão from Serviços Farmacêuticos do Centro Hospitalar de Lisboa Ocidental (CHLO, E.P.E.) for kindly offering us the paclitaxel used in this study and the Spanish National Cancer Research Center, CNIO (Madrid, Spain) for kindly donating the murine melanoma B16V5 cell line. The authors would also like to thank IT Jiménez from the Cell Culture Unit from University of Alcalá de Henares (UAH) for the help with the cell culture studies. Also, the authors would like to thank Spanish National Research Council (CSIC) for conducting XPS analysis.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Financial & competing interests disclosure

The authors thank Fundação para a Ciência e Tecnologia (FCT) for the partial financial support under the project reference PTDC/BBB-BMC/0611/2012. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.