Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-25T12:18:45.946Z Has data issue: false hasContentIssue false
  • English
  • Français

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: mariaangeles.gomezmorales@iss.it
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Amadi, B., Mwiya, S., Sianongo, S., Payne, L., Watuka, A., Katubulushi, M. and Kelly, P. (2009). High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial. BMC Infectious Diseases 2, 195.CrossRefGoogle Scholar
Askin, D. (1998). The synthesis of indinavir and other clinically useful HIV-1 protease inhibitors. Current Opinion in Drug Discovery & Development 1, 338–348.Google ScholarPubMed
Battegay, M., Fehr, J., Flückiger, U. and Elzi, L. (2008). Antiretroviral therapy of late presenters with advanced HIV disease. Journal of Antimicrobial Chemotherapy 62, 41–44.CrossRefGoogle ScholarPubMed
Batycky, R. P., Hanes, J., Langer, R. and Edwards, D. A. (1997). A theoretical model of erosion and macromolecular release from biodegrading microspheres. Journal of Pharmaceutical Science 86, 1464–1477.CrossRefGoogle ScholarPubMed
Bobin, S., Bouhouere, D., Dumpt, S., Boibieux, A., Grault, V. and Peyrnamond, D. (1998). Importance of antiprotease in the treatment of microsporidia and/or cryptosporidia infections in HIV-sero positive patients. Pathologie-Biologie 46, 418–419.Google ScholarPubMed
Cacciò, S., Pinter, E., Fantini, R., Mezzaroma, I. and Pozio, E. (2002). Human infection with Cryptosporidium felis: case report and literature review. Emerging Infectious Diseases 8, 85–86.CrossRefGoogle ScholarPubMed
Cho, K., Wang, X., Nie, S., Chen, Z. and Shin, D. M. (2008). Therapeutic nanoparticles for drug delivery in cancer. Clinical Cancer Research 14, 1310–1316.CrossRefGoogle ScholarPubMed
Cohen, S., Yoshioka, T., Lucarelli, M., Huang, L. H. and Langer, R. (1991). Controlled delivery systems for proteins based on poly (lactic/glycolic acid) microspheres. Pharmaceutical Research 8, 713–720.CrossRefGoogle ScholarPubMed
Costantino, L., Gandolfi, F., Bossy-Nobs, L., Tosi, G., Gurny, R., Rivasi, F., Vandelli, M. A. and Forni, F. (2006). Nanoparticulate drug carriers based on hybrid poly(d,l-lactide-co-glycolide)-dendron structures. Biomaterials 27, 4635–4645.CrossRefGoogle ScholarPubMed
Dimitrov, D. S., Feng, Y. and Prabakaran, P. (2008). Antibody-guided nanoparticles. Journal of Computational and Theoretical Nanoscience 5, 751–759.CrossRefGoogle Scholar
Dou, H., Destache, C. J., Morehead, J. R., Mosley, R. L., Boska, M. D., Kingsley, J., Gorantla, S., Poluektova, L., Nelson, J. A., Chaubal, M., Werling, J., Kipp, J., Rabinow, B. E. and Gendelman, H. E. (2006). Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. Blood 108, 2827–2835.CrossRefGoogle ScholarPubMed
Ethelberg, S., Lisby, M., Vestergaard, L. S., Enemark, H. L., Olsen, K. E., Stensvold, C. R., Nielsen, H. V., Porsbo, L. J., Plesner, A. M. and Mølbak, K. (2009). A foodborne outbreak of Cryptosporidium hominis infection. Epidemiology and Infection 137, 348–356.CrossRefGoogle ScholarPubMed
Fessi, H., Puisieux, F., Devissaguet, J. P., Ammoury, N. and Benita, S. (1989). Nanocapsule formation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics 55, R1–R4.CrossRefGoogle Scholar
Gagné, J. F., Désormeaux, A., Perron, S., Tremblay, M. J. and Bergeron, M. G. (2002). Targeted delivery of indinavir to HIV-1 primary reservoirs with immunoliposomes. Biochimica et Biophysica Acta 1558, 198–210.CrossRefGoogle ScholarPubMed
Gargala, G. (2008). Drug treatment and novel drug target against Cryptosporidium. Parasite 15, 275–281.CrossRefGoogle ScholarPubMed
Gref, R., Couvreur, P., Barratt, G. and Mysiakine, E. (2003). Surface-engineered nanoparticles for multiple ligand coupling. Biomaterials 24, 4529–4537.CrossRefGoogle ScholarPubMed
Gut, J. and Nelson, R. G. (1999). Cryptosporidium parvum: syncronized excystation in vitro and evaluation of sporozoite infectivity with a new Lectin-Based Assay. Journal of Eukaryotic Microbiology 46, 56S–57S.Google Scholar
Harush-Frenkel, O., Altschuler, Y. and Benita, S. (2008). Nanoparticle-cell interactions: drug delivery implications. Critical Reviews in Therapeutics Drug Carrier Systems 25, 485–544.CrossRefGoogle ScholarPubMed
Hommer, V., Eichholz, J. and Petry, F. (2003). Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cryptosporidium parvum. Journal of Antimicrobial Chemotherapy 52, 359–364.CrossRefGoogle ScholarPubMed
Huang, X., Chestang, B. L. and Brazel, C. S. (2002). Minimization of initial burst in poly(vinyl alcohol) hydrogels by surface extraction and surface-preferential crosslinking. International Journal of Pharmaceutics 248, 183–192.CrossRefGoogle ScholarPubMed
Hunter, P. R., Hughes, S., Woodhouse, S., Raj, N., Syed, Q., Chalmers, R. M., Verlander, N. Q. and Goodacre, J. (2004). Health sequelae of human cryptosporidiosis in immunocompetent patients. Clinical Infectious Diseases 39, 504–510.CrossRefGoogle ScholarPubMed
Huwlyer, J., Wu, D. and Pardridge, W. M. (1996). Brain drug delivery of small molecules using immunoliposomes. Proceedings of the National Academy of Sciences, USA 93, 14164–14169.CrossRefGoogle Scholar
Ives, N. J., Gazzard, B. G. and Easterbrook, P. J. (2001). The changing pattern of AIDS-defining illness with the introduction of highly active antiretroviral therapy (HAART) in a London clinic. Journal of Infection 42, 134–139.CrossRefGoogle Scholar
Jancis, B., Medenica, M., Ivanovic, D. and Malenovic, A. (2005). Evaluation of a liquid chromatographic method for analysis of Indinavir and degradation products arising from hydrolysis of its amide bond. Chromatographia 62, 233–238.CrossRefGoogle Scholar
Jao, J. and Wyatt, C. M. (2010). Antiretroviral medications: adverse effects on the kidney. Advances in Chronic Kidney Disease 17, 72–82.CrossRefGoogle ScholarPubMed
Mele, R., Gómez-Morales, M. A., Tosini, F. and Pozio, E. (2003). Indinavir reduces Cryptosporidium parvum infection in both in vitro and in vivo models. International Journal for Parasitology 33, 757–764.CrossRefGoogle ScholarPubMed
Miao, Y. M., Awad-El-Kariem, F. M., Franzen, C., Ellis, D. S., Müller, A., Counihan, H. M., Hayes, P. J. and Gazzard, B. G. (2000). Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy. Journal of Acquired Immune Deficiency Syndrome 25, 124–129.CrossRefGoogle ScholarPubMed
Mor, S. M. and Tzipori, S. (2008). Cryptosporidiosis in children in Sub-Saharan Africa: a lingering challenge. Clinical Infectious Diseases 47, 915–921.CrossRefGoogle ScholarPubMed
Motta, I., Gissot, M., Kanellopoulos, J. M. and Ojcius, D. M. (2002). Absence of weight loss during Cryptosporidium infection in susceptible mice deficient in Fas-mediated apoptosis. Microbes and Infection 4, 821–827.CrossRefGoogle ScholarPubMed
Nobs, L., Buchegger, F., Gurny, R. and Allemann, E. (2004). Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for active targeting. European Journal of Pharmaceutics and Biopharmaceutics 58, 483–490.CrossRefGoogle ScholarPubMed
Nobs, L., Buchegger, F., Gurny, R. and Allemann, E. (2003). Surface modification of poly-lactide acid nanoparticles by covalent attachment of thiol groups by means of three methods. International Journal of Pharmaceutics 250, 327–337.CrossRefGoogle ScholarPubMed
Pereira de Oliveira, M., Garcion, E., Venisse, N., Benoit, J. P., Couet, W. and Olivier, J. C. (2005). Tissue distribution of Indinavir administered as solid lipid nanocapsule formulation in mdr1a(+/+) and mdr1a(−/−) CF-1 mice. Pharmaceutical Research 22, 1898–1905.CrossRefGoogle Scholar
Plutzer, J. and Karanis, P. (2009). Genetic polymorphism in Cryptosporidium species: an update. Veterinary Parasitology 165, 187–199.CrossRefGoogle ScholarPubMed
Pozio, E. and Gómez-Morales, M. A. (2005). The impact of HIV-protease inhibitors on opportunistic parasites. Trends in Parasitology 21, 58–63.CrossRefGoogle ScholarPubMed
Rafati, H., Coombes, A. G. A., Adler, A., Holland, J. and Davis, S. S. (1997). Protein-loaded poly (DL-lactide-co-glycolide) microparticles for oral administration: formulation, structural and release characteristics. Journal of Controlled Release 43, 89–102.CrossRefGoogle Scholar
Ranucci, L., Muller, H. M., La Rosa, G., Reckman, I., Gomez Morales, M. A., Spano, F., Pozio, E. and Crisanti, A. (1993). Characterization and immunolocalization of a Cryptosporidium parvum protein containing repeated amino acids motifs. Infection and Immunity 61, 2347–2356.CrossRefGoogle Scholar
Rossi, P., Pozio, E., Besse, M. G., Gómez-Morales, M. A. and La Rosa, G. (1990). Experimental cryptosporidiosis in hamsters. Journal of Clinical Microbiology 28, 356–357.CrossRefGoogle ScholarPubMed
Rossignol, J. F. (2010). Cryptosporidium and Giardia: Treatment options and prospects for new drugs. Experimental Parasitolotogy 184, 103–106.Google Scholar
Sah, H. K., Toddywala, R. and Chien, Y. W. (1994). The influence of biodegradable microcapsule formulations on the controlled release of a protein. Journal of Controlled Release 30, 201–211.CrossRefGoogle Scholar
Sanvinvens, N. and Pilar, M. M. (2008). Multifunctional nanoparticles –properties and prospects for their use in human medicine. Trends in Biotechnology 26, 425–433.CrossRefGoogle Scholar
Slifko, T. R., Hoffman, D. E. and Rose, J. B. (1999). A most probable number assay for enumeration of infectious Cryptosporidium parvum oocysts. Applied and Enviromental Microbiology 65, 3936–3941.CrossRefGoogle ScholarPubMed
Torchilin, V. P. (2006). Multifunctional nanocarriers. Advanced Drug Delivery Reviews 58, 1532–1555.CrossRefGoogle ScholarPubMed
Tosi, G., Costantino, L., Ruozi, B., Forni, F. and Vandelli, M. A. (2008). Polymeric nanoparticles for the drug delivery to the central nervous system. Expert Opinion in Drug Delivery 5, 155–174.CrossRefGoogle ScholarPubMed
Uchida, K., Yagi, A., Oda, Y. and Goto, S. (1996). Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by and oil-in-oil (o/o) solvent evaporation method. Journal of Microencapsulation 13, 509–518.CrossRefGoogle Scholar
Upton, S. J., Tilley, M. and Brillhart, D. B. (1995). Effect of select medium supplements on in vitro development of Cryptosporidium parvum in HCT-8 cells. Journal of Clinical Microbiology 33, 371–375.CrossRefGoogle ScholarPubMed
Violari, A., Cotton, M. F., Gibb, D. M., Babiker, A. G., Steyn, J., Madhi, S. A., Jean-Philippe, P., McIntyre, J. A. and CHER Study Team. (2008). Early antiretroviral therapy and mortality among HIV-infected infants. The New England Journal of Medicine 20, 2233–2244.CrossRefGoogle Scholar
Wang, A. Z., Gu, F., Zhang, L., Chang, J. M., Radovic-Moreno, A., Shaikh, M. R. and Farokhzad, O. C. (2008). Biofunctionalized targeted nanoparticles for therapeutic applications. Expert Opinion on Biological Therapy 8, 1063–1070.CrossRefGoogle ScholarPubMed
Xu, Z., Pilch, D. S., Srinivasan, A. R., Olson, W. K., Geacintov, N. E. and Breslauer, K. J. (1997). Modulation of nucleic acid structure by ligand binding induction of a DNA.RNA.DNA hybrid triplex by DAPI intercalation. Bioorganic and Medical Chemistry 5, 1137–1147.CrossRefGoogle ScholarPubMed
Zardi, E. M., Picardi, A. and Afeltra, A. (2005). Treatment of cryptosporidiosis in immunocompromised hosts. Chemotherapy 51, 193–196.CrossRefGoogle ScholarPubMed