Vesicular systems employing natural substances as promising drug candidates for MMP inhibition in glioblastoma: A nanotechnological approach

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Abstract

Glioblastoma multiforme (GBM), one of the most lethal Brain tumors, characterized by its high invasive nature and increased mortality rates forms a major bottleneck in transport of therapeutics across the Blood Brain Barrier (BBB). Matrix metalloproteinases (MMPs) are classified as enzymes, which are found to be up regulated in the Glioma tumor microenvironment and thus can be considered as a target for inhibition for curbing GBM. Many chemotherapeutics and techniques have been employed for inhibiting MMPs till now but all of them failed miserably and were withdrawn in clinical trials due to their inability in restricting the tumor growth or increasing the overall survival rates. Thus, the quest for finding the suitable MMP inhibitor is still on and there is a critical need for identification of novel compounds which can alter the BBB permeability, restrain tumor growth and prevent tumor recurrence. Currently, naturally derived substances are gaining widespread attention as tumor inhibitors and many studies have been reported by far highlighting their importance in restricting MMP expression thus serving as chemotherapeutics for cancer due to their minimal toxicity. These substances may serve as probable candidates for inhibiting MMP expression in GBM. However, targeting and delivering the inhibitor to its target site is an issue that needs to be overcome in order to attain maximum specificity and sustained release. The birth of nanotechnology served as a boon in delivering drugs to the most complicated areas thus paving way for Nano drug delivery. An efficient Nano carrier with ability to cross the BBB and competently kill the Glioma cells forms the prerequisite for GBM chemotherapy. Vesicular drug delivery systems are one such class of carriers, which have the capacity to release the drug at a predetermined rate at the target site thus minimizing any undesirable side effects. Exploiting vesicular systems as promising Nano drug carriers to formulate naturally derived substances, that can bypass the BBB and act as an inhibitor against MMPs in GBM is the main theme of this review.

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