Article
Binding Mechanism of Doxorubicin in Lon-Exchange Albumin Microcapsules

https://doi.org/10.1002/jps.2600760613Get rights and content

Abstract

The absorption efficiency of cross-linked albumin microcapsules was evaluated as a function of various experimental conditions in an attempt to elucidate the doxorubicin binding mechanism of these microcapsules. The amount of drug absorbed augmented with increasing doxorubicin concentration until saturation was reached. Neither a Langmuir nor a Freundlich isotherm relationship was observed, indicating that the fixation of doxorubicin on the microcapsule walls did not follow a common physical adsorption process. Decreasing the mean particle diameter of the microcapsules increased the absorption rate and the total amount of doxorubicin absorbed, as expected. The absorption rate was enhanced by the elevation of the stirring rate of the aqueous drug solution. Furthermore, the presence of electrolytes in this aqueous solution profoundly altered the absorption profile of doxorubicin. Increasing the NaCI concentration in the solution reduced the total amount of drug absorbed. Moreover, the nature of the cation used also affected the absorption profile. These results suggested that there is a competitive fixation of the cation on the binding sites (identified as R-COO groups) available to the drug molecules. The weakly cross-linked microcapsules acted as cation-exchange resins which can exchange their labile sodium with the protonated drug present in the solution. This was also confirmed by the results of the titrimetric assay of the acidic microcapsules with NaOH.

References and notes (12)

  • F. Brasseur et al.

    Eur. J. Cancer

    (1980)
  • P. Couvreur et al.

    J. Pharm. Sci.

    (1982)
  • W.E. Longo et al.

    J. Pharm. Sci.

    (1982)
  • Y. Raghunathan et al.

    J. Pharm. Sci.

    (1981)
  • D.A. Schichting

    J. Pharm. Sci.

    (1962)
  • E.P. Goldberg et al.

    Microspheres and drug therapy. Pharmaceutical, Immunological and Medical Aspects

    (1984)
There are more references available in the full text version of this article.

Cited by (27)

  • Fabrication and evaluation of cationic exchange nanofibers for controlled drug delivery systems

    2013, International Journal of Pharmaceutics
    Citation Excerpt :

    The co-ion is carried along with it in order to maintain electroneutrality, until the chemical potentials are balanced (Jaskari et al., 2001). This phenomenon has also been observed with ion-exchange resins into which the amount of drugs loaded was significantly higher than the amount of ionic binding sites in resins when the highly concentrated drug solutions were loaded (Sawaya et al., 1987). The maximum loading of propranolol in Amberlite™ IRP 69 resin (4.4 mmol/g) was higher than the IEC of resin (3.45 meq/g).

  • Lyophilisomes as a new generation of drug delivery capsules

    2012, International Journal of Pharmaceutics
    Citation Excerpt :

    This effect cannot be explained by the process of simple diffusion. Albumin is known as an important transport protein and has several binding sites for hydrophobic compounds, which may explain the affinity of albumin for doxorubicin, maintaining the drug within lyophilisomes (Sawaya et al., 1987; Dreis et al., 2007). Albumin-based lyophilisomes may be a suitable delivery system for this drug and doxorubicin loaded lyophilisomes may be prepared upfront and stored at 4 °C or in a lyophilized state.

  • The effect of valence on the ion-exchange process: Theoretical and experimental aspects on compound binding/release

    2007, Journal of Pharmaceutical Sciences
    Citation Excerpt :

    The release of di-COOH was consistently lower than the release of SA across the used fibers and external conditions. The electrostatic interaction between the bound divalent compound and the ion-exchanger is stronger as compared with the monovalent compound (SA) due to the dual site binding.15,21–25 The formed strong interaction hinders the release of di-COOH from the fibers, especially in the case of monovalent extracting electrolyte, by preferring the divalent di-COOH over the chloride-ion (electroselectivity) (Tab. 3,

View all citing articles on Scopus
View full text