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Formulation and Characterization of Bioactive Agent Containing Nanodisks
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Formulation and Characterization of Bioactive Agent Containing Nanodisks

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Toxicity of an effective amphotericin B formulation at high cationic lipid to drug molar ratio

Nilton Lincopan1, Primavera Borelli, Ricardo Fock

  • 1Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, Avenida Lineu Prestes 748 - Butantã, CEP 05513-970 São Paulo, Brazil.

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie
|September 20, 2006
PubMed

Insights

The novel DODAB/AMB formulation shows reduced kidney toxicity compared to Fungizone. However, the DODAB carrier caused spleen damage and liver effects, necessitating dose reduction in future studies.

Area of Science:

  • Pharmacology
  • Toxicology
  • Drug Delivery

Background:

  • Amphotericin B (AMB) is a vital antifungal, but its nephrotoxicity limits use.
  • Novel formulations aim to improve AMB's therapeutic index.
  • Dioctadecyldimethylammonium bromide (DODAB) bilayer fragments offer a potential AMB delivery system.

Purpose of the Study:

  • To evaluate the toxicity of a DODAB/AMB formulation in mice.
  • To compare its toxicity profile with the conventional DOC/AMB (Fungizone).
  • To assess long-term effects on spleen, liver, and kidneys.

Main Methods:

  • Swiss Webster female mice received intraperitoneal injections of DODAB, DODAB/AMB, or DOC/AMB for 10 days.
  • Toxicity assessed via biochemical, hematological, and histopathological analyses on day 11 and after 6 months.
  • Specific focus on spleen, liver, and kidney damage.

Main Results:

  • DODAB/AMB demonstrated significantly less kidney toxicity than DOC/AMB.
  • DODAB administration, even within the formulation, led to irreversible spleen fibrosis and leukocyte infiltration.
  • DODAB caused focal liver necrosis at 6 months, while DOC/AMB induced more severe multifocal necrosis earlier and longer.
  • Most observed toxicities were attributed to the DODAB carrier at the tested concentration.

Conclusions:

  • The DODAB/AMB formulation is less nephrotoxic than DOC/AMB.
  • The DODAB carrier is responsible for observed spleen and liver toxicities.
  • Future research should focus on minimizing DODAB concentration to mitigate its side effects.

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