Nose-to-brain delivery of sorafenib-loaded lipid-based poloxamer-carrageenan nanoemulgel: Formulation and therapeutic investigation in glioblastoma-induced orthotopic rat model
Shubham Khot, Unmesh Mahajan, Amol Jadhav, Prajakta Vaishampayan, Uddhav S. Bagul, Dnyandev Gadhave, Bapi Gorain, Chandrakant Kokare
Abstract
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 50 (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.