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Chitosan-Stearic Acid Based Polymeric Micelles for the Effective Delivery of Tamoxifen: Cytotoxic and Pharmacokinetic Evaluation

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ABSTRACT

Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells. The conjugate was characterized by FT-IR and NMR, and the nanocarrier was characterized for micromeritics, surface charge, drug loading, and morphological attributes. The efficacy was evaluated by in vitro MTT studies, safety by erythrocyte compatibility, and biodistribution by in vivo pharmacokinetic studies. Despite better drug loading and sustained drug release, cytotoxicity on MCF-7 breast cancer cells was substantially enhanced and the pharmacokinetic profile was significantly modified. The AUC was enhanced manifolds along with reduced clearance. The findings are unique and provide an alternative to the conventional lipid-based nanocarriers for better dose delivery, tissue adhesion, and desired pharmacokinetic modulation.

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ACKNOWLEDGMENTS

The authors acknowledge the financial support from the University Grants Commission, New Delhi, India, in the form of UGC-Start-Up Grant to the corresponding author.

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Authors and Affiliations

  1. Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Kishangarh, Rajasthan, India, 305 817

    Nagarani Thotakura, Mukesh Dadarwal, Pramod Kumar & Kaisar Raza

  2. Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India, 160 014

    Gajanand Sharma & Om Prakash Katare

  3. Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu, India, 180001

    Santosh Kumar Guru & Shashi Bhushan

Authors
  1. Nagarani Thotakura
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  2. Mukesh Dadarwal
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  3. Pramod Kumar
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  4. Gajanand Sharma
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  5. Santosh Kumar Guru
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  6. Shashi Bhushan
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  7. Kaisar Raza
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  8. Om Prakash Katare
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Correspondence to Kaisar Raza.

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Thotakura, N., Dadarwal, M., Kumar, P. et al. Chitosan-Stearic Acid Based Polymeric Micelles for the Effective Delivery of Tamoxifen: Cytotoxic and Pharmacokinetic Evaluation. AAPS PharmSciTech 18, 759–768 (2017). https://doi.org/10.1208/s12249-016-0563-6

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  • DOI: https://doi.org/10.1208/s12249-016-0563-6

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