Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment
<b>Background/Objectives:</b> Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery resul...
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2024-11-01
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| author | Kendra Sorroza-Martínez Ignacio González-Sánchez Raúl Villamil-Ramos Marco Cerbón Jorge Antonio Guerrero-Álvarez Cristina Coronel-Cruz Ernesto Rivera Israel González-Méndez |
| author_facet | Kendra Sorroza-Martínez Ignacio González-Sánchez Raúl Villamil-Ramos Marco Cerbón Jorge Antonio Guerrero-Álvarez Cristina Coronel-Cruz Ernesto Rivera Israel González-Méndez |
| author_sort | Kendra Sorroza-Martínez |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. <b>Methods:</b> The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by <sup>1</sup>H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D<sub>2</sub>O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. <b>Results:</b> The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. <b>Conclusions:</b> The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment. |
| format | Article |
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| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-4bafc53e069b44e8a12e3209898ffa182024-12-27T14:46:20ZengMDPI AGPharmaceutics1999-49232024-11-011612150910.3390/pharmaceutics16121509Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer TreatmentKendra Sorroza-Martínez0Ignacio González-Sánchez1Raúl Villamil-Ramos2Marco Cerbón3Jorge Antonio Guerrero-Álvarez4Cristina Coronel-Cruz5Ernesto Rivera6Israel González-Méndez7Departamento de Sistemas Biológicos, Unidad Xochimilco, Universidad Autónoma Metropolitana, Calzada del Hueso 1100, Col. Villa Quietud, Mexico City CP 04960, MexicoDepartamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Escolar, Ciudad Universitaria, Mexico City CP 04510, MexicoCentro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca CP 62209, MexicoDepartamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Escolar, Ciudad Universitaria, Mexico City CP 04510, MexicoCentro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca CP 62209, MexicoDepartamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito Escolar, Ciudad Universitaria, Mexico City CP 04510, MexicoDepartamento de Reología, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Mexico City CP 04510, MexicoCentro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca CP 62209, Mexico<b>Background/Objectives:</b> Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. <b>Methods:</b> The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by <sup>1</sup>H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D<sub>2</sub>O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. <b>Results:</b> The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. <b>Conclusions:</b> The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment.https://www.mdpi.com/1999-4923/16/12/1509PAMAM dendrimerdoxorubicinbreast cancerinclusion complexβ-cyclodextrincontrolled release |
| spellingShingle | Kendra Sorroza-Martínez Ignacio González-Sánchez Raúl Villamil-Ramos Marco Cerbón Jorge Antonio Guerrero-Álvarez Cristina Coronel-Cruz Ernesto Rivera Israel González-Méndez Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment Pharmaceutics PAMAM dendrimer doxorubicin breast cancer inclusion complex β-cyclodextrin controlled release |
| title | Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment |
| title_full | Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment |
| title_fullStr | Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment |
| title_full_unstemmed | Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment |
| title_short | Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment |
| title_sort | using poly amidoamine pamam βcd dendrimer for controlled and prolonged delivery of doxorubicin as alternative system for cancer treatment |
| topic | PAMAM dendrimer doxorubicin breast cancer inclusion complex β-cyclodextrin controlled release |
| url | https://www.mdpi.com/1999-4923/16/12/1509 |
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