Nanoparticles of hydrophobized cluster dextrin as biodegradable drug carriers: solubilization and encapsulation of amphotericin B

Cluster dextrin (CDex), a highly branched cyclic dextrin, is a novel glucose polymer that is produced from a waxy corn starch by a branching enzyme. Despite its large molecular weight (462 kDa), CDex is highly water-soluble and is easily digested by enzymes, such as α-amylase. Amphotericin B (AmB) i...

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Bibliographic Details
Published in:Journal of drug delivery science and technology 2014-01, Vol.24 (4), p.344-351
Main Authors: Kaneo, Y., Taguchi, K., Tanaka, T., Yamamoto, S.
Format: Article
Language:English
Subjects:
Amphotericin B
Biodegradation
Biodisposition
Cluster dextrin
Nanoparticle
Saccharomyces cerevisiae
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Summary:Cluster dextrin (CDex), a highly branched cyclic dextrin, is a novel glucose polymer that is produced from a waxy corn starch by a branching enzyme. Despite its large molecular weight (462 kDa), CDex is highly water-soluble and is easily digested by enzymes, such as α-amylase. Amphotericin B (AmB) is a broad-spectrum fungicidal antibiotic used primarily in the treatment of life-threatening systemic fungal infections. Unfortunately, AmB is insoluble in water; therefore, we have attempted to render it soluble and transportable by encapsulating it in hydrophobized CDex nanoparticles. The amphiphilic polymers of CDex were prepared with hydrophobic groups bonded through ester bonds, and the degrees of substitution were 1.00 mol/mol % for n-octanoyl CDex, 1.80 mol/mol % for stearoyl CDex, 1.07 mol/mol % for oleoyl CDex, and 1.07 mol/ mol % for cholesteryl CDex. To study the formation of the monodispersed nanoparticles of the hydrophobized CDexs by self-assembly and their complex formations with AmB, size-exclusion chromatography and dynamic light scattering were utilized. AmB encapsulated in the cholesteryl CDex nanoparticle was found to be non-hemolytic, even at 30 μg/mL, which suggested that it had a much higher concentration than the minimum inhibitory concentration of 0.78 μg/mL required to inhibit Saccharomyces cerevisiae. Therefore, the biodistributions of the AmB-loaded cholesteryl CDex nanoparticles and AmBisome (liposomal AmB) were further compared in mice. After intravenous injection of the AmB-loaded cholesteryl CDex nanoparticle, prolonged persistence of AmB in the circulating blood was observed.
ISSN:1773-2247
DOI:10.1016/S1773-2247(14)50072-X