Polymeric Micellar Formulation Enhances Antimicrobial and Anticancer Properties of Salinomycin

  • Carolina Sousa
  • Luís F. Gouveia
  • Bruna Kreutzer
  • Beatriz Silva-Lima
  • Retsepile E. Maphasa
  • Admire Dube
  • Mafalda VideiraEmail author
Research Paper



Salinomycin (SAL) is a polyether compound that exhibits strong antimicrobial as well as anticancer activity. Nanomedicine has been at the forefront of drug delivery research with the aim of increasing the efficacy, specificity and reduce toxicity of drugs. There is an intersection between infection and cancer, and cancer patients are prone to bacterial infections. In this study, polymeric micelles were prepared using Pluronic® F127 (PM) to encapsulate SAL (PM_SAL) with the view of enhancing antimicrobial and anticancer activity.


A Quality by Design (QbD) approach was utilized to synthesize PM_SAL, and nanoformulation activity was determined against bacterial (S. aureus, MRSA and E. coli). Effects on cancer cell line A549, i.e. cell viability, prevention of P-gp efflux, vimentin expression, effects on migratory ability of A549 cells. Anticancer activity was determined by ability to eradicate cancer stem-like cells.


PM_SAL demonstrated only efficacy against MRSA, being even higher than that obtained with SAL. In A549 cells, a 15-fold increase in P-gp’s expression as well as a significant decrease of the cell’s migration, was observed.


PM_SAL can interfere with the oncogenic protein VIM, involved in the crucial mechanisms EMT, downregulating its expression. Altogether data obtained indicates that this antibiotic and the developed polymeric micelle system is a very promising inhibitor of tumor cell growth.


Antibiotics cancer stem cells nanomedicines polymeric micelles quality by design salinomycin 



ATP-binding cassette


Serine/threonine protein Kinase


Breast cancer resistance protein


Biopharmaceutical Classification System


Critical Material Attributes


Critical Process Parameters


Critical quality attributes


Cancer stem-like cells


Dynamic light scattering


2,4 Dinitrophenyl Hydrazine


Design of Experiments

E. coli

Escherichia coli


Encapsulation Efficiency


Epithelial to mesenchymal transition




International Conference on Harmonisation


Half Maximal Inhibitory concentration


Mean Diameter


Multidrug resistance




Multidrug resistance-associated protein 1


Methicillin-resistant Staphylococcus aureus


Polydispersity Index


Polyethylene Glycol




Phosphatidylinositol-4,5-bisphosphate 3-kinase


Pluronic® F127-based polymeric micelles


Polymeric micelles with encapsulated Salinomycin


Quality by Design


Quality Target product profile


Reticuloendothelial System


Room Temperature



S. aureus

Staphylococcus aureus


Standard Deviation


Trichloroacetic acid




Zeta Potential


Acknowledgments and Disclosures

Professor Mafalda Videira acknowledges the European Comission and the Fundação para a Ciência e Tecnologia (FCT), Portugal, for funding the projects “NanoGlio - Nanotechnology based immunotherapy for glioblastoma” (ENMed/0065/2016) and “Target4Cancer - (Nano) systems with active targeting to sensitize colorectal cancer stem cells to anti-tumoral treatment”. (ENMed/0009/2015): March 2016–2019″ and COST Action MP1404, “SimInhale”.

The work was funded, in part, by iMed.ULisboa (UID/DTP/04138/2013) from Fundação para a Ciência e a Tecnologia (FCT), Portugal.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pharmacological and Regulatory Sciences Group (PharmaRegSci), Research Institute for Medicines (iMed.ULisboa)Faculdadde de Farmácia da Universidade de LisboaLisbonPortugal
  2. 2.Discipline of Pharmaceutics, School of PharmacyUniversity of the Western CapeBellvilleSouth Africa
  3. 3.iMed.ULisboa – Research Institute for Medicines and Pharmaceutical Sciences, Faculty of PharmacyUniversity of LisbonLisbonPortugal

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