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Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application

Authors Moura CC, Segundo MA, das Neves J, Reis S, Sarmento B

Received 27 May 2014

Accepted for publication 10 July 2014

Published 23 October 2014 Volume 2014:9(1) Pages 4911—4922

DOI https://doi.org/10.2147/IJN.S68440

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Catarina Costa Moura,1,2 Marcela A Segundo,1 José das Neves,3,4 Salette Reis,1 Bruno Sarmento3,4

1REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Faculty of Engineering, University of Porto, Porto, Portugal; 3CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto de Ciências da Saúde-Norte, Gandra PRD, Portugal; 4INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal

Background: Rheumatoid arthritis (RA) is an autoimmune disease with severe consequences for the quality of life of sufferers. Regrettably, the inflammatory process involved remains unclear, and finding successful therapies as well as new means for its early diagnosis have proved to be daunting tasks. As macrophages are strongly associated with RA inflammation, effective diagnosis and therapy may encompass the ability to target these cells. In this work, a new approach for targeted therapy and imaging of RA was developed based on the use of multifunctional polymeric nanoparticles.
Methods: Poly(lactic-co-glycolic acid) nanoparticles were prepared using a single emulsion-evaporation method and comprised the co-association of superparamagnetic iron oxide nanoparticles (SPIONs) and methotrexate. The nanoparticles were further functionalized with an antibody against the macrophage-specific receptor, CD64, which is overexpressed at sites of RA. The devised nanoparticles were characterized for mean particle size, polydispersity index, zeta potential, and morphology, as well as the association of SPIONs, methotrexate, and the anti-CD64 antibody. Lastly, the cytotoxicity of the developed nanoparticles was assessed in RAW 264.7 cells using standard MTT and LDH assays.
Results: The nanoparticles had a mean diameter in the range of 130–200 nm and zeta potential values ranging from -32 mV to -16 mV. Association with either methotrexate or SPIONs did not significantly affect the properties of the nanoparticles. Conjugation with the anti-CD64 antibody, in turn, caused a slight increase in size and surface charge. Transmission electron microscopy confirmed the association of SPIONs within the poly(lactic-co-glycolic acid) matrix. Both anti-CD64 and methotrexate association were confirmed by Fourier transform infrared spectroscopy, and quantified yielding values as high as 36% and 79%, respectively. In vitro toxicity studies confirmed the methotrexate-loaded nanosystem to be more effective than the free drug.
Conclusion: Multifunctional anti-CD64-conjugated poly(lactic-co-glycolic acid) nanoparticles for the combined delivery of methotrexate and SPIONs were successfully prepared and characterized. This nanosystem has the potential to provide a new theranostic approach for the management of RA.

Keywords: FcγRI, methotrexate, poly(lactic-co-glycolic acid), superparamagnetic iron oxide nanoparticles, targeted drug delivery

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