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Effect of aggregation state on the toxicity of different amphotericin B preparations.
Int J Pharm. 2008 Sep 01; 361(1-2):64-9.IJ

Abstract

The aim of this work was to study the effect of aggregation of amphotericin B (AMB) in their toxicity. The aggregation of AMB depends on different formulation factors such as pH and excipients, therefore three formulations with different AMB aggregation states were prepared: a monomeric form (M-AMB), a dimeric form (D-AMB) and a poly-aggregated form (P-AMB). The predominant aggregation state of each AMB formulation was characterized by spectrophotometry and their size by dynamic laser light scattering. Toxicity was evaluated by lethality in mice and hemolysis test from human erythrocytes and the experimental AMB formulations were compared with reference formulations of AmBisome, Fungizone and heated Fungizone. The less toxic aggregation form of AMB was the poly-aggregated one which was similar to AmBisome. Moreover, the P-AMB and heated Fungizone were centrifuged to isolate different size fractions. The toxicity of these two heterogeneous formulations was related to their size, so the smaller the aggregation size fraction the higher the toxicity determined by hemolysis. It can be concluded that the aggregation state of AMB and their size affects critically the toxicity of AMB. The low toxic P-AMB formulations contain a different poly-aggregated state to that of AmBisome, heated Fungizone and the other studied AMB aggregation states.

Authors+Show Affiliations

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad Complutense, Madrid 28040, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18599228

Citation

Espada, Raquel, et al. "Effect of Aggregation State On the Toxicity of Different Amphotericin B Preparations." International Journal of Pharmaceutics, vol. 361, no. 1-2, 2008, pp. 64-9.
Espada R, Valdespina S, Alfonso C, et al. Effect of aggregation state on the toxicity of different amphotericin B preparations. Int J Pharm. 2008;361(1-2):64-9.
Espada, R., Valdespina, S., Alfonso, C., Rivas, G., Ballesteros, M. P., & Torrado, J. J. (2008). Effect of aggregation state on the toxicity of different amphotericin B preparations. International Journal of Pharmaceutics, 361(1-2), 64-9. https://doi.org/10.1016/j.ijpharm.2008.05.013
Espada R, et al. Effect of Aggregation State On the Toxicity of Different Amphotericin B Preparations. Int J Pharm. 2008 Sep 1;361(1-2):64-9. PubMed PMID: 18599228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of aggregation state on the toxicity of different amphotericin B preparations. AU - Espada,Raquel, AU - Valdespina,Suriñe, AU - Alfonso,Carlos, AU - Rivas,German, AU - Ballesteros,M Paloma, AU - Torrado,Juan J, Y1 - 2008/05/20/ PY - 2008/02/14/received PY - 2008/05/09/revised PY - 2008/05/12/accepted PY - 2008/7/5/pubmed PY - 2008/10/11/medline PY - 2008/7/5/entrez SP - 64 EP - 9 JF - International journal of pharmaceutics JO - Int J Pharm VL - 361 IS - 1-2 N2 - The aim of this work was to study the effect of aggregation of amphotericin B (AMB) in their toxicity. The aggregation of AMB depends on different formulation factors such as pH and excipients, therefore three formulations with different AMB aggregation states were prepared: a monomeric form (M-AMB), a dimeric form (D-AMB) and a poly-aggregated form (P-AMB). The predominant aggregation state of each AMB formulation was characterized by spectrophotometry and their size by dynamic laser light scattering. Toxicity was evaluated by lethality in mice and hemolysis test from human erythrocytes and the experimental AMB formulations were compared with reference formulations of AmBisome, Fungizone and heated Fungizone. The less toxic aggregation form of AMB was the poly-aggregated one which was similar to AmBisome. Moreover, the P-AMB and heated Fungizone were centrifuged to isolate different size fractions. The toxicity of these two heterogeneous formulations was related to their size, so the smaller the aggregation size fraction the higher the toxicity determined by hemolysis. It can be concluded that the aggregation state of AMB and their size affects critically the toxicity of AMB. The low toxic P-AMB formulations contain a different poly-aggregated state to that of AmBisome, heated Fungizone and the other studied AMB aggregation states. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/18599228/Effect_of_aggregation_state_on_the_toxicity_of_different_amphotericin_B_preparations_ DB - PRIME DP - Unbound Medicine ER -