Fabrication of a Thermosensitive In Situ Gel Nanoemulsion for Nose to Brain Delivery of Temozolomide

Abstract

In this study, a thermosensitive in situ gel nanoemulsion was formulated by a low energy method for intranasal delivery of temozolomide to bypass the blood-brain barrier and optimize chemotherapy for glioblastoma. Various amounts of Labrasol, Transcutol®P, and Triacetin were chosen as nanoemulsion components based on the solubility and the partial pseudoternary phase diagrams studies. Poloxamer derivatives added to the selected nanoemulsion and gelling temperature optimized. The prepared in situ gel nanoemulsion containing temozolomide showed a mean droplet size of 16.25 ± 0.44 nm , a polydispersity index value of 0.35 ± 0.01 , and desirable pH and viscosity. In vitro release studies revealed that both nanoemulsion and in situ gel preparation have sustained release pattern in comparison to the control solution. Visual evaluation and droplet size and polydispersity index measurements showed both nanoemulsion and in situ gel nanoemulsion were stable during heating-cooling and freeze-thaw cycles and also centrifugation. Mucoadhesion percentage of in situ gel nanoemulsion was 37.037 ± 2.32 regarding ex vivo studies, which had a significant rise in comparison to control solution and nanoemulsion. Permeation across the nasal mucosa was 1.43- and 1.52-fold higher than the control solution for nanoemulsion and in situ nanoemulsion, respectively. Gamma scintigraphy study showed brain accumulation of developed nanoemulsion formulations. Our studies demonstrated optimized formulation has suitable physicochemical properties, desirable release profile, enhanced permeation across the nasal mucosa, and prolonged resistance time at the nasal mucosa. Therefore, in situ gel nanoemulsion would be an effective novel nasal delivery system for the treatment of glioblastoma.

Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution

“…The effect of permeation enhancers appeared obvious in the investigation of Khan et al in which the presence of anethole in lipidic vesicles significantly boosted ursolic acid permeation through goat nasal mucosa due to its penetration enhancement characteristics in comparison with the control gel [ 52 ]. Labrasol ® influences the tight junction permeability which could also contribute to the enhanced nasal permeation of propranolol [ 55 ]. Moreover, the nano-sized vehicles expanded the surface area available for propranolol permeation through nasal mucosa, in addition to their ability to transport the drug through the epithelium cells via paracellular or transcellular pathways, particularly endocytosis [ 56 ].…”

Topical Nanoemulsion-Based Gel of Isoconazole Nitrate

“…UVspectrophotometry at the drug λmax wavelength which is 273 that used to determine the concentration of ISN in the sample media at each of these time points by using the equation of calibration curve shown in Figure (1) [26] [27].…”

Nose to brain delivery of drugs for CNS diseases

“…Furthermore, thermo-sensitive nasal in-situ gel was produced by Masoumeh et al This gel was loaded with a temozolomide nanoemulsion, and investigated for the treatment of glioblastoma through a direct nose to brain delivery (44). Based on the pseudo ternary phase diagrams, Labrasol, Transcutol, and Triacetin were selected to be the components of the nano emulsion.…”