In-Vitro, Ex-Vivo & In-Vivo Assessment of Brain Targeted Thermoreversible Mucoadhesive In-Situ Intranasal Gel of Carmustine for the Treatment of Glioblastoma

The goal of the present study was to prepare an in situ carmustine gel to evaluate the viability of brain targeting via nasal administration. Initial formulations (CG1–CG5) were made, and their varied medicinal properties were assessed. Polymers that were employed as mucoadhesive with thermoreversible materials were carbopol 934 and poloxamer 407 respectively. The gel formulations were made using a cold process. Using a visual technique, the phase transition temperature was determined. The in vitro release, ex vivo carmustine permeability via goat nasal mucosal membrane, pH, mucoadhesive strength, and in vivo pharmacokinetic studies of the gels were assessed. The purpose of the histological analysis of the nasal mucosal membrane was to look for signs of harmful effects caused by carmustine permeability. It was discovered that the 18.00 percentage w/v poloxamer mixture was exhibiting a phase change at physiological temperatures (34.00 to 35.00 °C). The gelling temperature was found to drop when the carbopol 934 proportion was raised as of 0.1– 0.5 percentage weight/volume. The mucoadhesive strength of every preparation was more than 3500 dynes/cm 2 . A study on carmustine permeation has shown that employing carbopol 934 at concentrations higher than 0.3% w/v can accelerate the rate of carmustine permeation. No indication of injury has been found in the histological investigation of the nasal mucosa following the carmustine permeation trial. Compared to commercial intravenous (IV) injections of carmustine, in vivo pharmacokinetic analysis of carmustine in situ gel revealed increased C max , AUC 0→ t , and AUC 0→∞ and lower T max (1 h) data in the brain. Hence, in situ thermoreversible mucoadhesive intranasal gel of carmustine might be an impactful therapy in the management of glioblastoma (GBM).