4.4 Article

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

期刊

AAPS PHARMSCITECH
卷 19, 期 1, 页码 460-469

出版社

SPRINGER
DOI: 10.1208/s12249-017-0851-9

关键词

tamoxifen; phytantriol; liquid crystalline nanoparticles; oral delivery; breast cancer

资金

  1. Science and Engineering Research Board (SERB), DST, GOI, New Delhi
  2. Council of Scientific and Industrial Research (CSIR), GOI, New Delhi

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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 (similar to 7- and similar to 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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