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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Perspective

Saponins-uptake and Targeting Issues for Brain-specific Delivery for Enhanced Cell Death Induction in Glioblastoma

Author(s): P.K. Suresh*

Volume 19, Issue 6, 2022

Published on: 31 March, 2022

Page: [473 - 480] Pages: 8

DOI: 10.2174/1570180819666220121145332

Abstract

Saponins represent a category of diverse, natural glycoside molecules that belong to the triterpenoid or the steroid class. They vary in terms of their solubility and permeability characteristics and are classifiable based on the biopharmaceutics classification system. They have drug delivery potential as surfactants that can solubilize cholesterol in the plasma membrane of tumorigenic cells. Glioblastoma is an important malignancy that can aggressively afflict the brain of humans with a poor prognosis. Glioblastoma Stem Cells (GSCs) are an important subset of cancer cells and major determinants for drug resistance and tumour relapse. These cells are quiescent and have been known to survive current therapeutic strategies. Certain saponins have shown potential to eliminate glioblastoma cells in a variety of model systems and hence provide a sound scientific basis for their development as a “stand-alone” drug or as part of a drug combination (from the existing arsenal of drugs) developed for the treatment of glioblastoma. However, due to their reactogenicity towards the immune system and hemolytic potential, selective delivery to the tumorigenic site is essential. Hence, nano-formulations (liposome/emulsion-based delivery systems/nano-structured lipid and calix[n]arenes-based carriers) and variants that are resistant to saponin may serve as delivery tools that can be functionalized to improve the selectivity. It is necessary to develop/ validate/refine in vitro higher order models that replicate the features of the glioma microenvironment (BBB/BTB). Reproducible validation of the model as well as the drug/delivery system will help in the development of formulations that can augment cell death in this recalcitrant brain tumour.

Keywords: Saponins, liposomes, targeting, brain-specific delivery, cell death, glioblastoma.

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