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Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus\u00ae (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg\/mL) and\/or PTX (4 mg\/mL). Their micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 70 and 90 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells rendering optimal antitumor efficacy in both cell lines for the nanoformulations with both drugs. In a model of TNBC developed in BALB\/c mice with 4T1 cells, we found that all loaded micellar systems reduced tumor volume and that both HA and HA-PTX-loaded SG micelles reduced tumor weight and neovascularization compared with the empty micelles. We conclude that HA-PTX co-loaded micelles in addition to HA-loaded formulations present promising potential as nano-drug delivery systems for cancer chemotherapy.<\/jats:p>","DOI":"10.3390\/ijms24043546","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:56:13Z","timestamp":1675997773000},"page":"3546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nanomicellar Formulations Loaded with Histamine and Paclitaxel as a New Strategy to Improve Chemotherapy for Breast Cancer"],"prefix":"10.3390","volume":"24","author":[{"given":"Melisa B.","family":"Nicoud","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio A.","family":"Ospital","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica A.","family":"T\u00e1quez Delgado","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Riedel","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Tecnolog\u00eda Farmac\u00e9utica I, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Instituto de Tecnolog\u00eda Farmac\u00e9utica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Fuentes","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Tecnolog\u00eda Farmac\u00e9utica I, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Instituto de Tecnolog\u00eda Farmac\u00e9utica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Tecnolog\u00eda Farmac\u00e9utica I, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Instituto de Tecnolog\u00eda Farmac\u00e9utica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-5975","authenticated-orcid":false,"given":"Mara R.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Laboratorio de Psiconeuroendocrinoinmunolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Lauretta","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Mart\u00ednez Vivot","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda de los \u00c1ngeles","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Salgueiro","sequence":"additional","affiliation":[{"name":"Instituto de Tecnolog\u00eda Farmac\u00e9utica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Laboratorio de Radiois\u00f3topos, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Speisky","sequence":"additional","affiliation":[{"name":"Servicio de Patolog\u00eda, Hospital Brit\u00e1nico de Buenos Aires, Buenos Aires 1280, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela A.","family":"Moretton","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Tecnolog\u00eda Farmac\u00e9utica I, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Instituto de Tecnolog\u00eda Farmac\u00e9utica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Chiappetta","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Tecnolog\u00eda Farmac\u00e9utica I, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Instituto de Tecnolog\u00eda Farmac\u00e9utica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanina A.","family":"Medina","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tumoral e Inflamaci\u00f3n, Instituto de Investigaciones Biom\u00e9dicas (BIOMED), Facultad de Ciencias M\u00e9dicas, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1107, Argentina"},{"name":"Laboratorio de Radiois\u00f3topos, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, October 17). 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