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Salinomycin-loaded PLA nanoparticles: drug quantification by GPC and wave voltammetry and biological studies on osteosarcoma cancer stem cells

Analytical and Bioanalytical Chemistry volume 412, pages 4681–4690 (2020)Cite this article

Abstract

A new straightforward gel permeation chromatography (GPC) method was developed to calculate the drug encapsulation efficiency and loading content of Poly(lactic acid) nanoparticles (PLA NPs) loaded with Salinomycin (Sal), exploiting the capability of this technique to separate a macromolecular/molecular mixture on the basis of the molecular weight of each component. The proposed GPC method allowed Sal detection until 1% of Sal content in PLA NPs, avoiding sample pre-treatments. The method was validated by wave voltammetry (SW) technique, using a slightly modified literature procedure, useful to detect Sal in the concentration range 0.4 ≤ C/μmol/L ≤ 12 (linear concentration range). PLA-based NPs were prepared by nanoprecipitation with either native and functionalized PLA. Specifically, folate-decorated PLA NPs (PLA-FA NPs) were obtained by CuAAC click functionalization of alkyne-grafted PLA with azide-folate. Sal-loaded NPs were characterized physicochemically and morphologically. They exhibited adequate physicochemical properties, good drug encapsulation efficiency (98 ± 0.5% and 99 ± 0.5%), and loading content (8.8 ± 0.1% and 8.9 ± 0.1% for PLA/Sal and PLA-FA/Sal NPs, respectively). The size of empty PLA NPs resulted smaller (90 ± 3.2 nm and 680 ± 15.3 nm, for PLA NPs and PLA-FA NPs respectively) than the correspondent drug-loaded NPs (110 ± 3.8 nm and 875 ± 20.5 nm, respectively). Their biological activity was assessed on osteosarcoma bulk cells MG63, healthy osteoblast cell line (hFOB1.19), and enriched osteosarcoma cancer stem cells (CSCs), showing cell-depending effect. Entrapped Sal maintained its cytotoxic effect on CSCs and MG63 cells, with a potency comparable to the free drug and no evident benefit was detected for folate-decorated PLA NPs respect to native PLA NPs.

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Authors and Affiliations

  1. Department of Chemical Sciences, University of Catania, V.le A.Doria, 95125, Catania, Italy

    Placido G. Mineo & Fabiana Vento

  2. Institute of Polymers, Composites and Biomaterials CNR-IPCB, Via P. Gaifami 18, I-95126, Catania, Italy

    Placido G. Mineo

  3. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166, Messina, Italy

    Claudia Foti, Anna Piperno & Angela Scala

  4. CNR-ISTEC, Institute of Science and Technology for Ceramics, National Research Council of Italy, Via Granarolo, 64, 48018, Faenza (RA), Italy

    Monica Montesi & Silvia Panseri

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  1. Placido G. Mineo
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  2. Claudia Foti
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Correspondence to Angela Scala.

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Mineo, P.G., Foti, C., Vento, F. et al. Salinomycin-loaded PLA nanoparticles: drug quantification by GPC and wave voltammetry and biological studies on osteosarcoma cancer stem cells. Anal Bioanal Chem 412, 4681–4690 (2020). https://doi.org/10.1007/s00216-020-02721-6

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  • DOI: https://doi.org/10.1007/s00216-020-02721-6

Keywords

  • Poly(lactic acid)
  • Nanoparticles
  • Gel permeation chromatography
  • Voltammetry
  • Folate
  • Cancer stem cells