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

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:579

Article

Tasca, Elisamaria¹  Andreozzi, Patrizia^2,3  Del Giudice, Alessandra¹  Galantini, Luciano^1,4  Schillen, Karin⁵  Giuliani, Anna Maria⁶  de los Angeles Ramirez, Maria²  Enrique Moya, Sergio²  Giustini, Mauro^1,4 

[1] Univ Roma La Sapienza, Chem Dept, Ple Aldo Moro 5, I-00185 Rome, Italy

[2] Basque Res & Technol Alliance BRTA, Ctr Cooperat Res Biomat CIC BiomaGUNE, Paseo Miramon 182, Donostia San Sebastian 20014, Spain

[3] Univ Florence, Chem Dept Hugo Shiff, Via Lastruccia 13, I-50019 Florence, Italy

[4] Univ Aldo Moro, Chem Dept, CSGI Operat Unit Bari, Ctr Colloid & Surface Sci, Ban, Italy

[5] Lund Univ, Dept Chem, Div Phys Chem, POB 124, SE-22100 Lund, Sweden

[6] Univ Palermo, STEBICEF Dept, Palermo, Italy

关键词: Drug-delivery;    Doxorubicin hydrochloride;    PEO-PPO-PEO block copolymers;    Pluronics;    Bile salts;    Tumour cell lines;    Confocal microscopy;   

DOI  :  10.1016/j.jcis.2020.06.096

来源: Elsevier

【 摘 要 】

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. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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