Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, India.
Department of Chemistry, Baburaoji Gholap College (affiliated to Savitribai Phule Pune University), Sangvi, Pune 411027, Maharashtra, India.
Int J Biol Macromol. 2021 Jan 15;167:906-920. doi: 10.1016/j.ijbiomac.2020.11.047. Epub 2020 Nov 10.
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 μg/cm, 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. IC was found 7.0 μg/mL for TNLCGHG, 4.8 μg/mL for pure TFM, and 78.5 μg/mL for TNLC, which approve the superiority of surfactant along with gellan gum as permeation enhancer. Brain C for technetium (TC) labeled intranasal (i.n.) TC-TNLCGHG was found 2-folds higher than TC-TNLC (i.n.) and TC-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.
本研究旨在制备替西罗莫司（TFM）负载的纳米脂质体（TNLC）卡波姆-结冷胶原位凝胶（TNLCGHG），并研究其对脑和脊柱肿瘤胶质母细胞瘤的治疗效果。纳米制剂采用结冷胶和卡波姆 974P 分别作为凝胶和粘膜粘附剂，甘醇二硬脂酸酯和甘醇单亚油酸酯混合物作为脂质，Gelucire 44/14：水混合物作为表面活性剂系统。结果发现，胶粒大小、PDI、Zeta 电位、包封效率、粘膜粘附强度和鼻渗透分别为 117.80nm、0.56、-21.86mV、81.16%、4.80g 和 904μg/cm。在人 U-87MG 胶质母细胞瘤细胞系中测定了载替西罗莫司的纳米脂质体卡波姆-结冷胶原位凝胶（TNLCGHG）的抗癌效果。发现 TNLCGHG 的 IC 为 7.0μg/mL，纯 TFM 的 IC 为 4.8μg/mL，TNLC 的 IC 为 78.5μg/mL，这证明了表面活性剂与结冷胶作为渗透增强剂的优越性。锝（TC）标记的经鼻（i.n.）TC-TNLCGHG 的脑 C 比 TC-TNLC（i.n.）和 TC-TNLC 静脉内（i.v.）高 2 倍，因为 TNLCGHG 制剂含有具有天然凝胶聚合物的表面活性剂，这有希望提高药物渗透性。最后，这项研究揭示了令人鼓舞的结果，并成功开发了经鼻 TNLCGHG 纳米制剂，作为胶质母细胞瘤患者安全输送 TFM 的新工具。
