Dually Active Apigenin-Loaded Nanostructured Lipid Carriers for Cancer Treatment

Abstract

Lorena Bonilla-Vidal,1,2 Marta Świtalska,3 Marta Espina,1,2 Joanna Wietrzyk,3 Maria Luisa García,1,2 Eliana B Souto,4,5 Anna Gliszczyńska,6,* Elena Sánchez López1,2,7,* 1Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, University of Barcelona, Barcelona, Spain; 2Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain; 3Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland; 4Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 5Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal; 6Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Wrocław, Poland; 7Unit of Synthesis and Biomedical Applications of Peptides, IQAC-CSIC, Barcelona, Spain*These authors contributed equally to this workCorrespondence: Elena Sánchez López; Anna Gliszczyńska, Email [email protected]; [email protected]: Cancer is one of the major causes of death worldwide affecting more than 19 million people. Traditional cancer therapies have many adverse effects and often result in unsatisfactory outcomes. Natural flavones, such as apigenin (APG), have demonstrated excellent antitumoral properties. However, they have a low aqueous solubility. To overcome this drawback, APG can be encapsulated in nanostructured lipid carriers (NLC). Therefore, we developed dual NLC encapsulating APG (APG-NLC) with a lipid matrix containing rosehip oil, which is known for its anti-inflammatory and antioxidant properties.Methods: Optimisation, physicochemical characterisation, biopharmaceutical behaviour, and therapeutic efficacy of this novel nanostructured system were assessed.Results: APG-NLC were optimized obtaining an average particle size below 200 nm, a surface charge of − 20 mV, and an encapsulation efficiency over 99%. The APG-NLC released APG in a sustained manner, and the results showed that the formulation was stable for more than 10 months. In vitro studies showed that APG-NLC possess significant antiangiogenic activity in ovo and selective antiproliferative activity in several cancer cell lines without exhibiting toxicity in healthy cells.Conclusion: APG-NLC containing rosehip oil were optimised. They exhibit suitable physicochemical parameters, storage stability for more than 10 months, and prolonged APG release. Moreover, APG-NLC were internalised inside tumour cells, showing the capacity to cause cytotoxicity in cancer cells without damaging healthy cells.Keywords: antitumoral, lipid nanoparticles, apigenin, rosehip oil

Keywords

• antitumoral
• lipid nanoparticles
• apigenin
• rosehip oil.