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<p>Titanium dioxide (TiO<sub>2</sub>) enhanced chitosan nanoparticles with para-coumaric acid (PCA) payload was designed to mitigate leishmaniasis. Both PCA and TiO<sub>2</sub> were reported to inhibit growth of both amastigotes and promastigotes of <i>Leishmania donovani</i> through metabolic interventions. Nanoparticle design was perceived to meet biopharmaceutical drawbacks of PCA for improved therapeutic outcomes with TiO<sub>2</sub>-assisted selectivity for macrophages. PCA loaded nanoparticles were prepared with biopolymer chitosan following ionotropic gelation technique. Nanoparticles exhibited a quasi-spherical shape in FESEM with size 417.6 ± 40.2&#xa0;nm, PDI of 0.217 ± 0.01 and Zeta potential of 72.3 ± 5.9&#xa0;mV. PCA entrapment was found to be 73.33% and its release was sustained for 12&#xa0;h. MTT assay derived IC<sub>50</sub> values of engineered NPs against <i>Leishmania</i> promastigotes, <i>Leishmania</i> amastigotes and RAW 267.4 cell lines were 11.7 ± 0.74, 14.2 ± 0.6 and 34.9 ± 0.1&#xa0;μg/ml respectively clearly indicating the increased efficacy of the engineered NPs against both the lifecycle stages of <i>Leishmania</i>. The selectivity index of the engineered NP was 2.92 compared to 1.83 for free PCA confirming for its attractive potential for clinical translation. Designed nanoparticles with fast and increased cellular uptake can be a smarter option for leishmaniasis management targeting the parasites with negligible toxicity against normal cells indicating the specificity of the intervention.</p> Graphic Abstract <p></p>

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Metal Oxide–Enhanced Para-Coumaric Acid Nanoparticles for Precision Targeting of Leishmania donovani

  • 期刊论文

  • 发表日期：

    2025年1月7日

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  • Kartikesh Sahu,
  • Raj Amrit Singh Samant,
  • Tiasha Routh,
  • Sriparna Bawali,
  • Sumanta Mondal,
  • Arunima Biswas,
  • Suvadra Das,
  • Partha Roy

摘要

Titanium dioxide (TiO2) enhanced chitosan nanoparticles with para-coumaric acid (PCA) payload was designed to mitigate leishmaniasis. Both PCA and TiO2 were reported to inhibit growth of both amastigotes and promastigotes of Leishmania donovani through metabolic interventions. Nanoparticle design was perceived to meet biopharmaceutical drawbacks of PCA for improved therapeutic outcomes with TiO2-assisted selectivity for macrophages. PCA loaded nanoparticles were prepared with biopolymer chitosan following ionotropic gelation technique. Nanoparticles exhibited a quasi-spherical shape in FESEM with size 417.6 ± 40.2 nm, PDI of 0.217 ± 0.01 and Zeta potential of 72.3 ± 5.9 mV. PCA entrapment was found to be 73.33% and its release was sustained for 12 h. MTT assay derived IC50 values of engineered NPs against Leishmania promastigotes, Leishmania amastigotes and RAW 267.4 cell lines were 11.7 ± 0.74, 14.2 ± 0.6 and 34.9 ± 0.1 μg/ml respectively clearly indicating the increased efficacy of the engineered NPs against both the lifecycle stages of Leishmania. The selectivity index of the engineered NP was 2.92 compared to 1.83 for free PCA confirming for its attractive potential for clinical translation. Designed nanoparticles with fast and increased cellular uptake can be a smarter option for leishmaniasis management targeting the parasites with negligible toxicity against normal cells indicating the specificity of the intervention.

Graphic Abstract