Khot Shubham, Mahajan Unmesh, Jadhav Amol, Vaishampayan Prajakta, Bagul Uddhav, Gadhave Dnyandev, Gorain Bapi, Kokare Chandrakant
Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India.
Institute of Applied Biological Research and Development, (IABRD), A division of Nirav Biosolutions Pvt Ltd, Aundh, Pune 411007, Maharashtra, India.
Int J Biol Macromol. 2025 May;309(Pt 1):142861. doi: 10.1016/j.ijbiomac.2025.142861. Epub 2025 Apr 4.
Glioblastoma multiforme (GBM) has a poor clinical prognosis, where conventional treatment offers therapeutic limitations. Therefore, the current study introduces a first-of-its-kind sorafenib (SOR) nanoemulsion (SNE) loaded with poloxamer-carrageenan nanoemulgel (SPCNEG), a novel dual-functional and natural polymer-based payload system for effective intranasal chemotherapeutic administration. The nanoformulation was developed using carrageenan (a natural gelling agent), poloxamer (a mucoadhesive agent), glyceryl caprate as lipid, and Cremophor EL:PEG 400 blend as surfactant system. The improved biopharmaceutical attributes of developed formulations were confirmed from the release experiments, revealing augmentation in drug release from SNE (84.56 ± 3.78 %) and SPCNEG (68.62 ± 4.11 %) up to 3.41- and 8.12-fold compared to plain SOR. The ex vivo experiments showed a similar enhancement in drug permeation. Moreover, the SNE also showed superior performance on glioma cell lines, as indicated by lower IC (2.23 μg/mL) than plain SOR (16.61 μg/mL). The pharmacokinetic study revealed a 2.52- and 3.24-fold increase in SNE and SPCNEG brain concentration, respectively, compared to Soranib®. Additionally, a high correlation was also observed between in vitro drug release and in vivo absorption at prespecified time intervals for developed formulations. In conclusion, the current research promising and non-invasive alternative to existing interventions for enhanced brain targeting potential.
多形性胶质母细胞瘤（GBM）临床预后较差，传统治疗存在治疗局限性。因此，本研究首次引入了一种载有泊洛沙姆-卡拉胶纳米乳凝剂（SPCNEG）的索拉非尼（SOR）纳米乳剂（SNE），这是一种新型的基于天然聚合物的双功能有效鼻内化疗给药载体系统。该纳米制剂采用卡拉胶（一种天然胶凝剂）、泊洛沙姆（一种粘膜粘附剂）、癸酸甘油酯作为脂质以及聚氧乙烯蓖麻油：聚乙二醇400混合物作为表面活性剂系统研制而成。从释放实验证实了所研制制剂改善的生物药剂学特性，结果显示SNE（84.56±3.78%）和SPCNEG（68.62±4.11%）的药物释放量相较于普通SOR分别提高了3.41倍和8.12倍。体外实验表明药物渗透也有类似增强。此外，SNE在胶质瘤细胞系上也表现出优异性能，其IC（2.23μg/mL）低于普通SOR（16.61μg/mL）。药代动力学研究表明，与多吉美相比，SNE和SPCNEG的脑内浓度分别提高了2.52倍和3.24倍。此外，在所研制制剂的预定时间间隔内，体外药物释放与体内吸收之间也观察到高度相关性。总之，当前研究为现有干预措施提供了一种有前景的、非侵入性的替代方法，具有增强的脑靶向潜力。
