title: The loading of labelled antibody-engineered nanoparticles with Indinavir increases its in vitro efficacy against Cryptosporidium parvum.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bondioli
authors.forename: A
authors.initials: A
authors.lastname: Ludovisi
authors.forename: G
authors.initials: G
authors.lastname: Tosi
authors.forename: B
authors.initials: B
authors.lastname: Ruozi
authors.forename: F
authors.initials: F
authors.lastname: Forni
authors.forename: E
authors.initials: E
authors.lastname: Pozio
authors.forename: M A
authors.initials: MA
authors.lastname: Vandelli
authors.forename: M A
authors.initials: MA
authors.lastname: Gómez-Morales
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry; D002417:Cattle; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D019469:Indinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry; D008856:Microscopy, Fluorescence; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012235:Rhodamines / Q000032:analysis; D013057:Spectrum Analysis
chemical_list: D000913:Antibodies, Protozoan; D001672:Biocompatible Materials; D004337:Drug Carriers; D017320:HIV Protease Inhibitors; D018796:Immunoconjugates; D012235:Rhodamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019469:Indinavir; C005358:tetramethylrhodamine