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Parasitology ; 138(11): 1384-91, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21819637

RESUMO

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.


Assuntos
Química Farmacêutica/métodos , Criptosporidiose/tratamento farmacológico , Cryptosporidium parvum/efeitos dos fármacos , Portadores de Fármacos/química , Inibidores da Protease de HIV/farmacocinética , Imunoconjugados/farmacocinética , Indinavir/farmacocinética , Terapia de Alvo Molecular , Nanopartículas/química , Animais , Anticorpos Antiprotozoários/química , Anticorpos Antiprotozoários/imunologia , Materiais Biocompatíveis/química , Bovinos , Linhagem Celular Tumoral , Criptosporidiose/imunologia , Criptosporidiose/parasitologia , Composição de Medicamentos , Inibidores da Protease de HIV/uso terapêutico , Humanos , Imunoconjugados/química , Imunoconjugados/imunologia , Indinavir/uso terapêutico , Ácido Láctico/química , Microscopia de Fluorescência , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Rodaminas/análise , Análise Espectral
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