Formulation of Chitosan Nanoparticles Loaded with Metronidazole for the Treatment of Infectious Diseases
Jose L. Arias,
Gema I. Martinez-Soler,
M. Adolfina Ruiz.
Conventional chemotherapy of intracellular infections often fails due to the low uptake of commonly used antibiotics or to their reduced activity at the acidic pH of lysosomes. With the aim of improving the therapeutic action of metronidazole against intracellular infections along with an overcome of their important drawbacks, we investigated its incorporation into a drug delivery nanosystem based on the biodegradable polymer chitosan. The formulation of this polymeric colloid assured a high electric surface charge and a great hydrophobicity, which are known to be two important characteristics determining an intense and non-specific recognition by the mononuclear phagocyte system (i.e., rapid uptake by infected phagocytes). Two metronidazole loading procedures were investigated: i) drug surface deposition or adsorption method onto already formed nanoparticles; and ii) drug absorption or entrapment into the polymeric matrix: incorporation of metronidazole prior to the coacervation process that leads to the formation of chitosan nanoparticles. Such polymeric colloid hold very significant characteristics (high drug loading and little burst release, hydrophobicity and high surface charge), suggesting its potential application for an efficient metronidazole delivery to intracellular infections.
Keywords: Chitosan, Drug carriers, Drug delivery, Intracellular infections, Metronidazole, Mononuclear phagocyte system
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