Comparative assessment of macrophage responses and antileishmanial efficacy in dynamic vs. Static culture systems utilizing chitosan-based formulations.

Alaa Riezk ORCID logo ; Alec O'Keeffe ; Katrien Van Bocxlaer ; Vanessa Yardley ORCID logo ; Simon L Croft ; (2025) Comparative assessment of macrophage responses and antileishmanial efficacy in dynamic vs. Static culture systems utilizing chitosan-based formulations. PloS one, 20 (3). e0319610-. ISSN 1932-6203 DOI: 10.1371/journal.pone.0319610
Copy

The discovery of novel anti-leishmanial compounds is essential due to the limitations of current treatments and the lack of new drugs in development. In this study, we employed the Quasi Vivo 900 medium perfusion system (QV900, Kirkstall Ltd, UK) to simulate physiological fluid flow, allowing us to compare macrophage responses and therapeutic outcomes under dynamic versus static conditions. After 24 hours, phagocytosis and macropinocytosis decreased in all cell types under flow conditions compared to static cultures. Under slow (1.45 x 10-9 m/s) and faster (1.23 x 10-7 m/s) flow conditions ((simulating in vivo lymphatic flow), phagocytosis decreased by around 42.55% and 56.98% in peritoneal macrophages (PEMs), 42.21% and 56.11% in bone marrow-derived macrophages (BMMs), and 49.75% and 63.32% in THP-1 cells, respectively. Similarly, macropinocytosis decreased by approximately 40.7% and 62.2% in PEMs, 34.8% and 60.9% in BMMs, and 33.3% and 59.3% in THP-1 cell line under this same conditions. In this study, we further assessed the impact of medium perfusion on drug efficacy and macrophage functions using a Leishmania major amastigote-macrophage assay. We evaluated the performance of both standard and nanoparticle-based drug formulations within dynamic and static culture systems. After 72 hours of medium perfusion, chitosan solution, blank chitosan-sodium tripolyphosphate (TPP) nanoparticles, and amphotericin B (AmB)-loaded chitosan-TPP nanoparticles exhibited a statistically significant reduction in antileishmanial activity by approximately 30-50% under slow flow conditions and 60-80% under faster flow conditions. In comparison, pure AmB showed a 40% decrease in efficacy at slow flow and a 67% decrease at faster flow, both statistically significant. These results highlighted the importance of considering fluid flow dynamics in in vitro studies for a more accurate simulation of in vivo conditions, potentially leading to better therapeutic strategies for cutaneous leishmaniasis (CL).

picture_as_pdf

picture_as_pdf
Riezk-etal-2025-comparative-assessment-of-macrophage-responses-and-antileshmanial-efficacy-in-dynamic-vs-static-culture-systems-utilizing-chitosan-based-formulations.pdf
subject
Published Version
Available under Creative Commons: Attribution 4.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads