Nose-to-brain delivery of teriflunomide-loaded lipid-based carbopol-gellan gum nanogel for glioma: Pharmacological and in vitro cytotoxicity studies

The research work was intended to formulate teriflunomide (TFM) loaded nano lipid-based (TNLC) carbopol-gellan gum in situ gel (TNLCGHG) and to investigate its therapeutic efficacy against glioma, a brain and spine tumor. Nanoformulation was developed using gellan gum and carbopol 974P as gelling and mucoadhesive agents, respectively, Glyceryl di-behenate and Glyceryl mono-linoleate blend as lipids, and Gelucire 44/14: water blend as surfactant system. Globule size, PDI, zeta potential, encapsulation efficiency, mucoadhesive strength, and nasal permeation were found to be 117.80 nm, 0.56, -21.86 mV, 81.16%, 4.80 g, and 904 mu g/cm(2), respectively. Anticancer efficacy of TFM-loaded nano lipid-based carbopol-gellan gum in situ gel (TNLCGHG) was determined in human U-87MG glioma cell line. IC50 was found 7.0 mu g/mL for TNLCGHG, 4.8 mu g/mL for pure TFM, and 78.5 mu g/mL for TNLC, which approve the superiority of surfactant along with gellan gum as permeation enhancer. Brain Cmax for technetium ((TC)-T-99m) labeled intranasal (i.n.) (TC)-T-99m-TNLCGHG was found 2-folds higher than (TC)-T-99m-TNLC (i.n.) and (TC)-T-99m-TNLC intravenous (i.v.) because the TNLCGHG formulation contains surfactant with natural gelling polymers, which promisingly improved drug permeability. Finally, this research revealed encouraging outcomes and successfully developed intranasal TNLCGHG nanoformulation as a novel tool for safe delivery of TFM in glioma patients. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The study successfully developed a novel nano lipid-based carbopol-gellan gum in situ gel for the safe delivery of teriflunomide in glioma patients. The formulation showed promising permeability enhancement and significant therapeutic efficacy.