Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery : An in-vitro bioavailability study
(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
- Tasca, Elisamaria ; Andreozzi, Patrizia ; Del Giudice, Alessandra LU ; Galantini, Luciano ; Schillén, Karin LU ; Maria Giuliani, Anna ; Ramirez, Maria de los Angeles ; Moya, Sergio Enrique and Giustini, Mauro
- organization
- publishing date
- 2020
- 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}}, }