Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery: An in-vitro bioavailability study

Elisamaria Tasca, Patrizia Andreozzi, Alessandra Del Giudice, Luciano Galantini, Karin Schillén, Anna Maria Giuliani, Maria de los Angeles Ramirez, Sergio Enrique Moya, Mauro Giustini

Research output: Contribution to journalArticlepeer-review

9 Citations (SciVal)

Abstract

Hypothesis: Doxorubicin hydrochloride (DX) is widely used as a chemotherapeutic agent, though its severe side-effects limit its clinical use. A way to overcome these limitations is to increase DX latency through encapsulation in suitable carriers. However, DX has a high solubility in water, hindering encapsulation. The formulation of DX with sodium cholate (NaC) will reduce aqueous solubility through charge neutralization and hydrophobic interactions thus facilitating DX encapsulation into poloxamer (F127) micelles, increasing drug latency. Experiments: DX/NaC/PEO-PPO-PEO triblock copolymer (F127) formulations with high DX content (DX-PMs) have been prepared and characterized by scattering techniques, transmission electron microscopy and fluorescence spectroscopy. Cell proliferation has been evaluated after DX-PMs uptake in three cell lines (A549, Hela, 4T1). Cell uptake of DX has been studied by means of confocal laser scanning microscopy and flow cytometry. Findings: DX-PMs formulations result in small and stable pluronic micelles, with the drug located in the apolar core of the polymeric micelles. Cell proliferation assays show a delayed cell toxicity for the encapsulated DX compared with the free drug. Data show a good correlation between cytotoxic response and slow DX delivery to nuclei. DX-PMs offer the means to restrict DX delivery to the cell interior in a highly stable and biocompatible formulation, suitable for cancer therapy.

Original languageEnglish
Pages (from-to)551-561
Number of pages11
JournalJournal of Colloid and Interface Science
Volume579
DOIs
Publication statusPublished - 2020

Subject classification (UKÄ)

  • Medicinal Chemistry

Keywords

  • Bile salts
  • Confocal microscopy
  • Doxorubicin hydrochloride
  • Drug-delivery
  • PEO-PPO-PEO block copolymers
  • Pluronics
  • Tumour cell lines

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