Preparation and <i>in Vitro</i> Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives

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  • Kimura Kotaro
    Faculty of Pharmaceutical Sciences, Sojo University
  • Yamasaki Keishi
    Faculty of Pharmaceutical Sciences, Sojo University DDS Research Institute, Sojo University
  • Nakamura Hideaki
    Faculty of Pharmaceutical Sciences, Sojo University
  • Haratake Mamoru
    Faculty of Pharmaceutical Sciences, Sojo University DDS Research Institute, Sojo University
  • Taguchi Kazuaki
    Faculty of Pharmaceutical Sciences, Sojo University
  • Otagiri Masaki
    Faculty of Pharmaceutical Sciences, Sojo University DDS Research Institute, Sojo University

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  • Highlighted Paper selected by Editor-in-Chief : Preparation and in Vitro Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives

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Abstract

<p>Nanoparticles prepared using human serum albumin (HSA) have emerged as versatile carriers for improving the pharmacokinetic profile of drugs. The desolvation of HSA using ethanol followed by stabilization through crosslinking with glutaraldehyde is a common technique for preparing HSA nanoparticles, but our knowledge concerning the characteristics (or functions) of HSA nanoparticles and their efficiency when loaded with drugs is limited. To address this issue in more detail, we prepared anthracycline-loaded HSA nanoparticles. Doxorubicin-loaded HSA nanoparticles with a size similar to doxorubicin-unloaded particles could be prepared by desolvating at a higher pH (8–9), and the size (100–150 nm) was optimum for delivery to tumor tissues. Using this procedure, HSA nanoparticles were loaded with other anthracycline derivatives, and all showed cytotoxicity in cancer cells. However, the efficiency of drug loading and dissolution rate were different among them possibly due to the differences in the type of association of the drugs on nanoparticles (doxorubicin and daunorubicin; covalently bound to nanoparticles, pirarubicin; both covalently bound to and adsorbed on nanoparticles, aclarubicin; adsorbed on nanoparticles). Since the formulation of such drug-loaded HSA nanoparticles should be modified for efficient delivery to tumors, the findings reported herein provide the useful information for optimizing the formulation and the production process for the HSA nanoparticles using a desolvation technique.</p>

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