Abstract
Amphotericin B (AmB) exhibits potential antileishmanial activity, with only a little rate of recurrence. However, low bioavailability and severe nephrotoxicity are among the major shortcomings of AmB-based therapy. Various AmB nanoformulations have been developed, which to an extent, have reduced its toxicity and increased the drug efficacy. To further reduce the nonspecific tissue distribution and the cost of the treatment, the current AmB-based formulations require additional improvements. Combination of natural bioenhancers with AmB is expected to further increase its bioavailability. Therefore, we developed a nanoformulation of AmB and piperine (Pip), a plant alkaloid, known to enhance the bioavailability of various drugs, by entrapping them in guar gum, a macrophage targeting polymer. Owing to the ease of oral delivery, these nanoparticles (NPs) were coated with eudragit to make them suitable for oral administration. The formulated eudragit-coated AmB and Pip-loaded NPs (Eu-HDGG-AmB-Pip-NPs) exhibited controlled release of the loaded therapeutic agents and protected the drug from acidic pH. These NPs exhibited effective suppression of growth of both promastigotes and amastigotes of Leishmania donovani parasite under in vitro. In vivo evaluation of these NPs for therapeutic efficacy in golden hamster-L. donovani model demonstrated enhanced drug bioavailability, non-nephrotoxic nature, and potential antileishmanial activity with up to 96% inhibition of the parasite.
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06 March 2020
In the original version of this article, Vikas Srivastava’s last name was spelled incorrectly.
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Acknowledgments
KCG thanks, Indian Council of Medical Research (ICMR), New Delhi, for awarding Dr. A.S. Paintal Distinguished Scientist Chair at CSIR-IGIB, Delhi. LR thanks CSIR, New Delhi, for her senior research associate (SRA) fellowship CSIR (Pool Section) (IA-27607) at CSIR-CDRI. NG acknowledges Council of Scientific and Industrial Research Network Project, HOPE (BSC0114) for financial support.
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Institutional Animal Ethics Committee (IAEC) of CSIR-Central Drug Research Institute, Lucknow, reviewed and approved the animal protocol [IAEC/2012/87/Renewed 05(5/13) and IAEC/2012/87/Renewed 06(15/14)] which was adhered to National guidelines CPCSEA (Committee For the Purpose of Control and Supervision of Experiments on Animals) of Government of India. Animals were housed in plastic cages at 23 ± 2 °C, humidity 60–63%, and fed standard rodent pellet and water ad libitum and fed with standard rodent food pellet (Lipton India, Bombay).
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The original version of the article has been corrected: Vikas Srivastava’s last name was spelled incorrectly.
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Ray, L., Karthik, R., Srivastava, V. et al. Efficient antileishmanial activity of amphotericin B and piperine entrapped in enteric coated guar gum nanoparticles. Drug Deliv. and Transl. Res. 11, 118–130 (2021). https://doi.org/10.1007/s13346-020-00712-9
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DOI: https://doi.org/10.1007/s13346-020-00712-9