Solid-State Formation of a Potential Melphalan Delivery Nanosystem Based on β-Cyclodextrin and Silver Nanoparticles

International Journal of Molecular Sciences, vol. 24, pp. 3990

Abstract

Melphalan (Mel) is an antineoplastic widely used in cancer and other diseases. Its low solubility, rapid hydrolysis, and non-specificity limit its therapeutic performance. To overcome these disadvantages, Mel was included in β-cyclodextrin (βCD), which is a macromolecule that increases its aqueous solubility and stability, among other properties. Additionally, the βCD–Mel complex has been used as a substrate to deposit silver nanoparticles (AgNPs) through magnetron sputtering, forming the βCD–Mel–AgNPs crystalline system. Different techniques showed that the complex (stoichiometric ratio 1:1) has a loading capacity of 27%, an association constant of 625 M−1, and a degree of solubilization of 0.034. Added to this, Mel is partially included, exposing the NH2 and COOH groups that stabilize AgNPs in the solid state, with an average size of 15 ± 3 nm. Its dissolution results in a colloidal solution of AgNPs covered by multiple layers of the βCD–Mel complex, with a hydrodynamic diameter of 116 nm, a PDI of 0.4, and a surface charge of 19 mV. The in vitro permeability assays show that the effective permeability of Mel increased using βCD and AgNPs. This novel nanosystem based on βCD and AgNPs is a promising candidate as a Mel nanocarrier for cancer therapy.

Authors 7

1. Rodrigo Sierpe

   Metropolitan University of Technology · University of Chile

   Affiliation as printed

   Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Sergio Livingstone #1007, Independencia, Santiago 8380492, Chile

   Departamento de Química, Facultad de Ciencias Naturales, Matemática y del Medio Ambiente, Universidad Tecnológica Metropolitana (UTEM), Las Palmeras 3360, Ñuñoa, Santiago 7800003, Chile

   Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras #3425, Ñuñoa, Santiago 7800003, Chile

2. Orlando Donoso-González Aachen Institute of Inorganic Chemistry

   Advanced Center for Chronic Diseases · University of Chile · RWTH Aachen University

   Affiliation as printed

   Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone #1007, Independencia, Santiago 8380492, Chile

   Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Sergio Livingstone #1007, Independencia, Santiago 8380492, Chile

   Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras #3425, Ñuñoa, Santiago 7800003, Chile

   Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1a, D-52074 Aachen, Germany

3. Erika Lang

   University of Chile

   Affiliation as printed

   Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras #3425, Ñuñoa, Santiago 7800003, Chile

4. Michael Noyong Aachen Institute of Inorganic Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1a, D-52074 Aachen, Germany

5. Ulrich Simon Aachen Institute of Inorganic Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1a, D-52074 Aachen, Germany

6. Marcelo Javier Kogan corresponding

   Advanced Center for Chronic Diseases · University of Chile

   Affiliation as printed

   Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone #1007, Independencia, Santiago 8380492, Chile

   Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Sergio Livingstone #1007, Independencia, Santiago 8380492, Chile

7. Nicolás Yutronic corresponding

   University of Chile

   Affiliation as printed

   Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras #3425, Ñuñoa, Santiago 7800003, Chile