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The loading of labelled antibody-engineered nanoparticles with Indinavir increases its in vitro efficacy against Cryptosporidium parvum

Published online by Cambridge University Press:  08 August 2011

L. BONDIOLI ,
A. LUDOVISI ,
G. TOSI ,
B. RUOZI ,
F. FORNI ,
E. POZIO ,
M. A. VANDELLI  and
M. A. GÓMEZ-MORALES
L. BONDIOLI
Affiliation:
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy
A. LUDOVISI
Affiliation:
Department of Infectious, Parasitic e Immunomediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
G. TOSI
Affiliation:
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy
B. RUOZI
Affiliation:
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy
F. FORNI
Affiliation:
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy
E. POZIO
Affiliation:
Department of Infectious, Parasitic e Immunomediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
M. A. VANDELLI
Affiliation:
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy
M. A. GÓMEZ-MORALES*
Affiliation:
Department of Infectious, Parasitic e Immunomediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
*
*Corresponding author: Department of Infectious, Parasitic e Immunomediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy. Tel: +39 06 4990 2078. Fax: +39 06 4990 3561. E-mail: [email protected]
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Summary

There is much evidence to indicate the ability of Indinavir (IND) to reduce Cryptosporidium parvum infection in both in vitro and in vivo models. However, there are limitations to the administration of IND as such, due to its renal toxicity and the high rate of metabolism and degradation. We aimed to encapsulate IND in biodegradable poly (D,L-lactide-co-glycolide) nanoparticles (Np) and to engineer their surface by conjugation with an anti-Cryptosporidium IgG polyclonal antibody (Ab). Tetramethylrhodamine-labelled Np were loaded with IND and modified by conjugation with an Ab. The IND-loaded modified Np (Ab-TMR-IND-Np) did not show any change, as demonstrated by chemical analysis studies. Simultaneous addition of 50μM Ab-TMR-IND-Np and excysted oocysts to the cell culture resulted in complete inhibition of the infection. In C. parvum-infected cells, the extent to which the infection decreased depended on the duration of treatment with the Ab-TMR-IND-Np. The antibody-engineered Np loaded with IND were able to target C. parvum in infected cells and therefore might represent a novel therapeutic strategy against Cryptosporidium sp. infection. Moreover, the use of Np as an IND delivery device, allows the development of a more appropriate dose formulation thereby reducing the IND side effects.

Keywords

Cryptosporidium parvumflow cytometryIndinavirnanoparticlesprotease inhibitors
Type
Research Article
Information
Parasitology , Volume 138 , Issue 11 , September 2011 , pp. 1384 - 1391
Copyright
Copyright © Cambridge University Press 2011

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