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Improved Oral Bioavailability, Therapeutic Efficacy, and Reduced Toxicity of Tamoxifen-Loaded Liquid Crystalline Nanoparticles

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Abstract

Present investigation deals with formulation and evaluation of tamoxifen (TMX)-loaded liquid crystalline nanoparticles (TMX-LCNPs) for improving oral bioavailability and safety of the existing treatment. Hexagonal Glyceryl monooleate-based TMX-LCNPs (GLCNPs) and Phytantriol-based TMX-LCNPs (PLCNPs) were prepared by dilution-through-hydrotrope method for oral administration. Oleic acid was incorporated in the lipid matrix to enhance the drug loading in the LCNPs. Optimized LCNPs displayed small particle size with a narrow distribution, sustained drug release and high gastrointestinal stability. TMX-LCNPs were found to be considerably higher cytotoxic to MCF-7 cells as compared to free TMX. Substantial fold enhancement in oral bioavailability (~7- and ~5-folds with TMX-GLCNPs and TMX-PLCNPs, respectively) was evident followed by significant reduction in tumor burden with lesser hepatotoxicity. Out of the two LCNP formulations, PLCNPs were found to be better in convalescing the disease.

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Acknowledgments

The authors are thankful to Director, NIPER for providing the necessary infrastructure and facilities. R.S is grateful to Science and Engineering Research Board (SERB), DST, GOI, New Delhi, for providing research fellowship. VK is grateful to Council of Scientific and Industrial Research (CSIR), GOI, New Delhi for providing fellowships.

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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, B. Heeralal, Rajan Swami, Nitin K. Swarnakar & Varun Kushwah

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  1. Sanyog Jain
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  2. B. Heeralal
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  3. Rajan Swami
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  4. Nitin K. Swarnakar
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  5. Varun Kushwah
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Correspondence to Sanyog Jain.

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Jain, S., Heeralal, B., Swami, R. et al. Improved Oral Bioavailability, Therapeutic Efficacy, and Reduced Toxicity of Tamoxifen-Loaded Liquid Crystalline Nanoparticles. AAPS PharmSciTech 19, 460–469 (2018). https://doi.org/10.1208/s12249-017-0851-9

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