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Lyotropic Liquid Crystalline Nanoparticles of Amphotericin B: Implication of Phytantriol and Glyceryl Monooleate on Bioavailability Enhancement

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Abstract

Implication of different dietary specific lipids such as phytantriol (PT) and glyceryl monooleate (GMO) on enhancing the oral bioavailability of amphotericin B (AmB) was examined. Liquid crystalline nanoparticles (LCNPs) were prepared using hydrotrope method, followed by in vitro characterization, Caco-2 cell monolayer uptake, and in vivo pharmacokinetic and toxicity evaluation. Optimized AmB-LCNPs displayed small particle size (< 210 nm) with a narrow distribution (~ 0.2), sustained drug release and high gastrointestinal stability, and reduced hemolytic toxicity. PLCNPs presented slower release, i.e., ~ 80% as compared to ~ 90% release in case of GLCNPs after 120 h. Significantly higher uptake in Caco-2 monolayer substantiated the role of LCNPs in increasing the intestinal permeability followed by increased drug titer in plasma. Pharmacokinetic studies demonstrated potential of PT in enhancing the bioavailability (approximately sixfold) w.r.t. of its native counterpart with reduced nephrotoxicity as presented by reduced nephrotoxicity biomarkers and histology studies. These studies established usefulness of PLCNPs over GLCNPs and plain drug. It can be concluded that acid-resistant lipid, PT, can be utilized efficiently as an alternate lipid for the preparation of LCNPs to enhance bioavailability and to reduce nephrotoxicity of the drug as compared to other frequently used lipid, i.e., GMO.

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Acknowledgments

The authors are grateful to the Director of NIPER for providing the required facilities and infrastructure. Rajan Swami is grateful to SERB, DST, GOI, New Delhi, for providing research fellowship. Varun Kushwah is appreciative to CSIR, GOI, New Delhi, for providing fellowships.

Funding

Authors are also thankful to the Department of Science & Technology (DST), GOI, New Delhi, for the financial support.

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Authors and Affiliations

  1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India

    Sanyog Jain, Pooja Yadav, Rajan Swami, Nitin Kumar Swarnakar, Varun Kushwah & Sameer S. Katiyar

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  1. Sanyog Jain
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  2. Pooja Yadav
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  3. Rajan Swami
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  6. Sameer S. Katiyar
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Correspondence to Sanyog Jain.

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All the animal study protocols were duly approved by Institutional Animal Ethics Committee (IAEC), NIPER, India.

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The authors declare that they have no conflict of interest.

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Jain, S., Yadav, P., Swami, R. et al. Lyotropic Liquid Crystalline Nanoparticles of Amphotericin B: Implication of Phytantriol and Glyceryl Monooleate on Bioavailability Enhancement. AAPS PharmSciTech 19, 1699–1711 (2018). https://doi.org/10.1208/s12249-018-0986-3

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