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Radiolabelled folate micellar carriers as proposed diagnostic aid for CNS tumors by nasal route

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Abstract

Glioma refers to the most atypical variant of the malignant central nervous system tumors posturing massive challenge to the research fraternity owing to the flimsy improvement in the patient survival rate over the past years. The aim of the proposed work was developing a diagnostic aid for brain tumors, which could be administered via the non-invasive intranasal route. Since overexpression of folate receptors in the central nervous system tumors is 500 times more than the normal healthy cells, we aimed at fabricating a radiolabeled folate encapsulated micellar delivery system to be given via the nasal route. Folate conjugated bifunctional chelating agent was synthesized, radiolabeled with 99mTc, and encapsulated in a micellar carrier. The fabricated micelles were further evaluated for in vivo nasal toxicity in rats and the same were found safe for intranasal administration. The fabricated micelles owing to their nano size, mucoadhesive nature, and enhanced permeation were observed to have a higher uptake into the brain (around 16% in 4 h) than as compared to the radiolabeled conjugated folate solution when studied for in vivo biodistribution in mice. Single-photon emission computerized tomography imaging performed in higher animals upon intranasal administration of the micellar formulation revealed enhanced uptake of the micelles into the animal brain. It is believed that the aforementioned formulation can be of a great diagnostic value in the detection of not only brain tumors but also other folate expressing cancers such as cervical, breast, and lungs as the system is fast, non-toxic, accurate, non-invasive, and simple.

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Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Board of Research in Nuclear Sciences, Department of Atomic Energy, Government of India (35/14/15/2015-BRNS).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, 400019, India

    Prashant Upadhaya & Vandana Patravale

  2. Division of Cyclotron and Radiopharmaceutical Sciences (DCRS), Institute of Nuclear Medicine and Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Timarpur, Delhi, 110054, India

    Puja Panwar Hazari & Anil Kumar Mishra

  3. Chemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, India

    Bijaideep Dutta & Puthusserickal Hassan

  4. Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India

    Bijaideep Dutta & Puthusserickal Hassan

Authors
  1. Prashant Upadhaya
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  2. Puja Panwar Hazari
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  3. Anil Kumar Mishra
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  4. Bijaideep Dutta
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  5. Puthusserickal Hassan
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  6. Vandana Patravale
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Correspondence to Vandana Patravale.

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The animal studies were performed as per the guidelines of the Institutional Animal Ethics Committee complying the current laws of the country.

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Upadhaya, P., Hazari, P.P., Mishra, A.K. et al. Radiolabelled folate micellar carriers as proposed diagnostic aid for CNS tumors by nasal route. Drug Deliv. and Transl. Res. 13, 2604–2613 (2023). https://doi.org/10.1007/s13346-023-01341-8

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  • DOI: https://doi.org/10.1007/s13346-023-01341-8

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