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Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

ABSTRACT: Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ?1 to ?45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer.

SUBMITTER: Di Francesco M

PROVIDER: S-EPMC7860091 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

Di Francesco Martina M Celia Christian C Cristiano Maria Chiara MC d'Avanzo Nicola N Ruozi Barbara B Mircioiu Constantin C Cosco Donato D Di Marzio Luisa L Fresta Massimo M

ACS omega 20210122 4

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinat ...[more]

PMID: 33553916

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Project description:BACKGROUND:Human platelets (PLT) and PLT-extracellular vesicles (PEV) released upon thrombin activation express receptors that interact with tumour cells and, thus, can serve as a delivery platform of anti-cancer agents. Drug-loaded nanoparticles coated with PLT membranes were demonstrated to have improved targeting efficiency to tumours, but remain impractical for clinical translation. PLT and PEV targeted drug delivery vehicles should facilitate clinical developments if clinical-grade procedures can be developed. METHODS:PLT from therapeutic-grade PLT concentrate (PC; N > 50) were loaded with doxorubicin (DOX) and stored at - 80 °C (DOX-loaded PLT) with 6% dimethyl sulfoxide (cryopreserved DOX-loaded PLT). Surface markers and function of cryopreserved DOX-loaded PLT was confirmed by Western blot and thromboelastography, respectively. The morphology of fresh and cryopreserved naïve and DOX-loaded PLT was observed by scanning electron microscopy. The content of tissue factor-expressing cancer-derived extracellular vesicles (TF-EV) present in conditioned medium (CM) of breast cancer cells cultures was measured. The drug release by fresh and cryopreserved DOX-loaded PLT triggered by various pH and CM was determined by high performance liquid chromatography. The thrombin activated PEV was analyzed by nanoparticle tracking analysis. The cellular uptake of DOX from PLT was observed by deconvolution microscopy. The cytotoxicities of DOX-loaded PLT, cryopreserved DOX-loaded PLT, DOX and liposomal DOX on breast, lung and colon cancer cells were analyzed by CCK-8 assay. RESULTS:15~36 × 106 molecules of DOX could be loaded in each PLT within 3 to 9 days after collection. The characterization and bioreactivity of cryopreserved DOX-loaded PLT were preserved, as evidenced by (a) microscopic observations, (b) preservation of important PLT membrane markers CD41, CD61, protease activated receptor-1, (c) functional activity, (d) reactivity to TF-EV, and (e) efficient generation of PEV upon thrombin activation. The transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX. CONCLUSIONS:Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.

Dataset Information

Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

Publications

Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

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