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

Tasca, Elisamaria ; Andreozzi, Patrizia ; Del Giudice, Alessandra LU orcid ; Galantini, Luciano ; Schillén, Karin LU orcid ; Maria Giuliani, Anna ; Ramirez, Maria de los Angeles ; Moya, Sergio Enrique and Giustini, Mauro (2020) In Journal of Colloid and Interface Science 579. p.551-561
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bile salts, Confocal microscopy, Doxorubicin hydrochloride, Drug-delivery, PEO-PPO-PEO block copolymers, Pluronics, Tumour cell lines
in
Journal of Colloid and Interface Science
volume
579
pages
11 pages
publisher
Elsevier
external identifiers
  • pmid:32623121
  • scopus:85087272367
ISSN
0021-9797
DOI
10.1016/j.jcis.2020.06.096
language
English
LU publication?
yes
id
1f56a6e7-ba75-489c-aa83-0eab47f2cd5d
date added to LUP
2020-07-14 11:42:59
date last changed
2024-04-17 12:43:04
@article{1f56a6e7-ba75-489c-aa83-0eab47f2cd5d,
  abstract     = {{<p>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.</p>}},
  author       = {{Tasca, Elisamaria and Andreozzi, Patrizia and Del Giudice, Alessandra and Galantini, Luciano and Schillén, Karin and Maria Giuliani, Anna and Ramirez, Maria de los Angeles and Moya, Sergio Enrique and Giustini, Mauro}},
  issn         = {{0021-9797}},
  keywords     = {{Bile salts; Confocal microscopy; Doxorubicin hydrochloride; Drug-delivery; PEO-PPO-PEO block copolymers; Pluronics; Tumour cell lines}},
  language     = {{eng}},
  pages        = {{551--561}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Colloid and Interface Science}},
  title        = {{Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery : An in-vitro bioavailability study}},
  url          = {{http://dx.doi.org/10.1016/j.jcis.2020.06.096}},
  doi          = {{10.1016/j.jcis.2020.06.096}},
  volume       = {{579}},
  year         = {{2020}},
}