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Development of reversible glutamine conjugate of methotrexate for enhanced brain delivery

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Abstract

Poor permeability of methotrexate across blood brain barrier limits its scope for application against brain cancer. Glutamine is transported to brain actively by multiple amino acid transporters and protects against complications of chemotherapy. To use glutamine as a carrier, a reversible conjugate of methotrexate was developed with structural features of glutamine. This was stable and released methotrexate effectively. The brain uptake was enhanced significantly

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Acknowledgments

The authors are thankful to Dr. Anil Kumar Mishra, HOD and Joint Director, Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi for his permission and Dr. Krushna Chuttani, Scientist, INMAS for her help in carrying out radioscintigraphy experiments. We are also thankful to Sophisticated Analytical Instrumentation Facility, Panjab University, Chandigarh for help in spectral characterisation and IPCA laboratories, Daman, India for providing methotrexate as gift sample.

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  1. Columbia Institute of Pharmacy, Raipur, 493111, Chhatishgarh, India

    Vijay Kumar Singh

  2. School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, 751003, Orissa, India

    Bharat Bhusan Subudhi

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  1. Vijay Kumar Singh
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Correspondence to Bharat Bhusan Subudhi.

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Singh, V.K., Subudhi, B.B. Development of reversible glutamine conjugate of methotrexate for enhanced brain delivery. Med Chem Res 24, 624–635 (2015). https://doi.org/10.1007/s00044-014-1172-0

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