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Long-term antitrypanosomal effect of quinapyramine sulphate-loaded oil-based nanosuspension in T. evansi-infected mouse model

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Abstract

The goal of the present work consisted of the formulation development and evaluation of quinapyramine sulphate (QS)-loaded long-acting oil-based nanosuspension for improved antitrypanosomal effect. QS was transformed into a hydrophobic ionic complex using anionic sodium cholate (Na.C). The complex was characterized by FTIR, DSC, and XRD. Oil-based nanosuspension was prepared by dispersing the QS-Na.C complex in thixotropically thickened olive oil. The nanoformulation was found to be cytocompatible (82.5 ± 5.87% cell viability at the minimum effective concentration [MEC]) in THP-1 cell lines and selectively trypanotoxic (p < 0.0001). The pharmacokinetic studies of QS-Na.C complex-loaded oily nanosuspension showed 13.54-fold, 7.09-fold, 1.78-fold, and 17.35-fold increases in t1/2, AUC0-∞, Vz/F, and MRT0-ꝏ, respectively, as compared to free QS. Moreover, a 7.08-fold reduction in plasma clearance was observed after the treatment with the optimized formulation in Wistar rats. Furthermore, treatment with QS-Na.C complex-loaded oily nanosuspension (7.5 mg/kg) in T. evansi-infected mice model showed the absence of parasitaemia for more than 75 days after the treatment during in vivo efficacy studies. The efficacy of the treatment was assessed by observation of blood smear and PCR assay for DNA amplification. To conclude, our findings suggest that the efficient delivery of QS from the developed QS-Na.C complex-loaded oily nanosuspension could be a promising treatment option for veterinary infections against trypanosomiasis.

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The datasets generated during the study are available from the corresponding authors upon request.

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Acknowledgements

Anil B. Jindal, Atish T. Paul, and Samar Kumar Ghorui are thankful to the Department of Biotechnology, Government of India, for providing financial support under the project (BT/PR18008/NNT/28/1055/2016). Kedar S. Prayag also thanks Birla Institute of Technology and Science Pilani, Pilani Campus, for providing fellowship.

Funding

This work was supported by the Department of Biotechnology, Government of India (BT/PR18008/NNT/28/1055/2016).

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Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Pilani Campus, 333031, Pilani, Jhunjhunu, Rajasthan, India

    Kedar S. Prayag, Atish T. Paul & Anil B. Jindal

  2. ICAR—National Research Centre on Camel, 334001, Jorbeer, Bikaner, Rajasthan, India

    Samar Kumar Ghorui

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  1. Kedar S. Prayag
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Contributions

Anil B. Jindal and Samar Kumar Ghorui have contributed to conceptualization and design of the studies in the present work. Kedar S. Prayag worked on formulation development, cell culture studies, in vitro antitrypanosomal activity against T. evansi, and in vivo pharmacokinetic experiments. Samar Kumar Ghorui developed the T. evansi-infected mouse model and carried out the in vivo efficacy experiments. Anil B Jindal, Samar Kumar Ghorui, and Atish T. Paul reviewed and edited the manuscript draft.

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Correspondence to Anil B. Jindal.

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Ethical approval

The study protocol for pharmacokinetic studies was approved by the Institutional Animal Ethics Committee of Birla Institute of Technology and Science, Pilani campus, Pilani, with Protocol no.: IAEC/RES/31/16, and for pre-clinical efficacy study, it was approved by the Institute Animal Ethics Committee of National Research Centre on Camels, Bikaner (vide No. NRCC/PSME/6/(141)2000-Tech).

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Prayag, K.S., Paul, A.T., Ghorui, S.K. et al. Long-term antitrypanosomal effect of quinapyramine sulphate-loaded oil-based nanosuspension in T. evansi-infected mouse model. Drug Deliv. and Transl. Res. 14, 542–554 (2024). https://doi.org/10.1007/s13346-023-01419-3

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