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Open AccessArticle

Production and Characterization of Chitosan–Polyanion Nanoparticles by Polyelectrolyte Complexation Assisted by High-Intensity Sonication for the Modified Release of Methotrexate

1
Department of Pharmacy, School of Pharmaceutical and Food Sciences, University of Antioquia, 67 Street No. 53-108, Medellín 050010, Colombia
2
Laboratorio de Diseño y Formulación de Productos Químicos y Derivados, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Naturales, Universidad ICESI, Calle 18 No. 122-135, Cali 760035, Colombia
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(1), 11; https://doi.org/10.3390/ph13010011
Received: 12 December 2019 / Revised: 3 January 2020 / Accepted: 5 January 2020 / Published: 8 January 2020
A promising strategy to improve the effectivity of anticancer treatment and decrease its side effects is to modulate drug release by using nanoparticulates (NPs) as carriers. In this study, methotrexate-loaded chitosan–polyanion nanoparticles were produced by polyelectrolyte complexation assisted by high-intensity sonication, using several anionic polymers, such as the sodium and potassium salts of poly(maleic acid-alt-ethylene) and poly(maleic acid-alt-octadecene), here named PAM-2 and PAM-18, respectively. Such NPs were analyzed and characterized according to particle size, polydispersity index, zeta potential and encapsulation efficiency. Likewise, their physical stability was tested at 4 °C and 40 °C in order to evaluate any change in the previously mentioned particle parameters. The in vitro methotrexate release was assessed at a pH of 7.4, which simulated physiological conditions, and the data were fitted to the heuristic models of order one, Higuchi, Peppas–Sahlin and Korsmeyer–Peppas. The results revealed that most of the MTX-chitosan–polyanion NPs have positive zeta potential values, sizes <280 nm and monodisperse populations, except for the NPs formed with PAM-18 polyanions. Further, the NPs showed adequate physical stability, preventing NP–NP aggregation. Likewise, these carriers modified the MTX release by an anomalous mechanism, where the NPs formed with PAM-2 polymer led to a release mechanism controlled by diffusion and relaxation, whereas the NPs formed with PAM-18 led to a mainly diffusion-controlled release mechanism. View Full-Text
Keywords: polyelectrolyte complexation; chitosan; poly (maleic acid-alt-ethylene), poly (maleic acid-alt-octadecene), methotrexate nanoparticles; polyelectrolyte complexation; modified release polyelectrolyte complexation; chitosan; poly (maleic acid-alt-ethylene), poly (maleic acid-alt-octadecene), methotrexate nanoparticles; polyelectrolyte complexation; modified release
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MDPI and ACS Style

Ciro, Y.; Rojas, J.; Alhajj, M.J.; Carabali, G.A.; Salamanca, C.H. Production and Characterization of Chitosan–Polyanion Nanoparticles by Polyelectrolyte Complexation Assisted by High-Intensity Sonication for the Modified Release of Methotrexate. Pharmaceuticals 2020, 13, 11.

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