Research Article

B cell-targeted polylactic acid nanoparticles as platform for encapsulating jakinibs: potential therapeutic strategy for systemic lupus erythematosus

https://orcid.org/0000-0002-1968-4647

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Universidad de Antioquia, Calle 70 No. 52–21 & Calle 62 No. 52–59, Torre 1, Lab. 510; Medellín, Colombia

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Juliana Palacio

https://orcid.org/0000-0001-8490-2113

Grupo De Investigación Ciencia de Los Materiales, Instituto de Química, Universidad de Antioquia, Calle 70 No. 52–21 & Calle 62 No. 52–59, Torre 1, Lab. 310; Medellín, Colombia

Escuela de Química, Universidad Nacional de Colombia, Sede Medellín, Carrera 65A No. 59A-110, Medellín, Colombia

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Natalia A Agudelo

https://orcid.org/0000-0002-7264-8303

Grupo de Investigación e Innovación en Formulaciones Químicas, Escuela de Ingeniería y Ciencias Básicas, Universidad EIA, Envigado, Colombia

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Cristian A Anacona

https://orcid.org/0000-0001-9176-939X

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Universidad de Antioquia, Calle 70 No. 52–21 & Calle 62 No. 52–59, Torre 1, Lab. 510; Medellín, Colombia

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Diana Castaño

https://orcid.org/0000-0002-5697-5603

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Universidad de Antioquia, Calle 70 No. 52–21 & Calle 62 No. 52–59, Torre 1, Lab. 510; Medellín, Colombia

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Gloria Vásquez

https://orcid.org/0000-0002-0647-0906

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Universidad de Antioquia, Calle 70 No. 52–21 & Calle 62 No. 52–59, Torre 1, Lab. 510; Medellín, Colombia

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Mauricio Rojas

*Author for correspondence: Tel.: +57 4219 6463;

E-mail Address: mauricio.rojas@udea.edu.co

https://orcid.org/0000-0002-7791-9328

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Universidad de Antioquia, Calle 70 No. 52–21 & Calle 62 No. 52–59, Torre 1, Lab. 510; Medellín, Colombia

Unidad de Citometría de Flujo, Sede de Investigación Universitaria, Universidad de Antioquia, Calle 62 No. 52–59, Medellín, 050010, Colombia

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Published Online:12 Dec 2023https://doi.org/10.2217/nnm-2023-0241

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Abstract

Background: B cells are pivotal in systemic lupus erythematosus and autoimmune disease pathogenesis. Materials & methods: To address this, Nile Red-labeled polylactic acid nanoparticles (NR-PLA NPs) loaded with the JAK inhibitor baricitinib (BARI), specifically targeting JAK1 and JAK2 in B cells, were developed. Results: Physicochemical characterization confirmed NP stability over 30 days. NR-PLA NPs were selectively bound and internalized by CD19⁺ B cells, sparing other leukocytes. In contrast to NR-PLA NPs, BARI-NR-PLA NPs significantly dampened B-cell activation, proliferation and plasma cell differentiation in healthy controls. They also inhibited key cytokine production. These effects often surpassed those of equimolar-free BARI. Conclusion: This study underscores the potential of PLA NPs to regulate autoreactive B cells, offering a novel therapeutic avenue for autoimmune diseases.

Plain language summary

In this study, a new approach to treating autoimmune diseases, particularly systemic lupus erythematosus, was investigated by focusing on a type of immune cell called B cells.

Special nanoparticles (NPs) labeled with Nile Red (NR) and made from polylactic acid (PLA) were created. These NPs were loaded with a drug called baricitinib (BARI), which targets specific proteins (JAK1 and JAK2) in B cells. This was done to determine if these NPs could help control the behavior of B cells, which are important in autoimmune diseases. First, these NPs remained stable for a long time (30 days). The NR-labeled PLA NPs (NR-PLA NPs) were also good at attaching to and entering a specific type of B cell called CD19⁺ B cells while leaving other types of immune cells alone. The use of NR-PLA NPs loaded with BARI produced exciting results. These NPs were better at reducing the activity, growth and transformation of B cells into plasma cells compared with the drug BARI by itself. They also stopped the production of certain immune system signals called cytokines, which are usually overactive in autoimmune diseases. This work suggests that PLA NPs could be a promising way to control overactive B cells that contribute to autoimmune diseases like systemic lupus erythematosus. This could open a new and exciting path for developing treatments for these conditions.

Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 18, No. 27

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Received 31 August 2023

Accepted 31 October 2023

Published online 12 December 2023

Published in print November 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0241

Author contributions

K Álvarez: Conceptualization, formal analysis, investigation, methodology, validation and writing of original draft. J Palacio: Methodology, formal analysis, writing, review, editing and methodology. NA Agudelo: Methodology, formal analysis, writing, review, editing and methodology. D Castaño: Methodology, writing, review, and editing. G Vásquez: Formal analysis, writing, review, editing and supervision. M Rojas: Conceptualization, funding acquisition, formal analysis, project administration, resources, writing of original draft and supervision.

Acknowledgments

The authors thank M Mesa for her English Language wording review and correction.

Financial disclosure

K Álvarez was a recipient of a doctoral scholarship from Universidad de Antioquia “Fondo Becas Doctoral UdeA”. This work was supported by Minciencias (grant number: 111584467267-925-2019) SOSTENIBILIDAD CODI. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

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