Intranasal Zolmitriptan-Loaded Bilosomes with Extended Nasal Mucociliary Transit Time for Direct Nose to Brain Delivery

Abstract

This study aimed at delivering intranasal zolmitriptan directly to the brain through preparation of bilosomes incorporated into a mucoadhesive in situ gel with extended nasal mucociliary transit time. Zolmitriptan-loaded bilosomes were constructed through a thin film hydration method applying Box–Behnken design. The independent variables were amount of sodium deoxycholate and the amount and molar ratio of cholesterol/Span® 40 mixture. Bilosomes were assessed for their entrapment efficiency, particle size and in vitro release. The optimal bilosomes were loaded into mucoadhesive in situ gel consisting of poloxamer 407 and hydroxypropyl methylcellulose. The systemic and brain kinetics of Zolmitriptan were evaluated in rats by comparing intranasal administration of prepared gel to an IV solution. Statistical analysis suggested an optimized bilosomal formulation composition of sodium deoxycholate (5 mg) with an amount and molar ratio of cholesterol/Span® 40 mixture of 255 mg and 1:7.7, respectively. The mucoadhesive in situ gel containing bilosomal formulation had a sol-gel temperature of 34.03 °C and an extended mucociliary transit time of 22.36 min. The gelling system possessed enhanced brain bioavailability compared to bilosomal dispersion (1176.98 vs. 835.77%, respectively) following intranasal administration. The gel revealed successful brain targeting with improved drug targeting efficiency and direct transport percentage indices. The intranasal delivery of mucoadhesive in situ gel containing zolmitriptan-loaded bilosomes offered direct nose-to-brain drug targeting with enhanced brain bioavailability.

Statistical Sequential Experimentation: Preliminary Mixed Factorial Design, I-Optimal Mixture Design Then Finally Novel Design Space Expansion for Optimization of Tazarotene Cubosomes

“…TEM was operated at 80 kv at room temperature and the morphological characters EMD-OF were inspected at proper magnifications. 46 …”

Investigating the Targeting Power to Brain Tissues of Intranasal Rasagiline Mesylate-Loaded Transferosomal In Situ Gel for Efficient Treatment of Parkinson’s Disease

“…Alternatively, there was non-significant difference in T max as C max was reached after 0.25 h for both groups. Concerning the AUC 0-12h , it was clear that the calculated values for IN in situ gel (27.31 ± 5.60 ng.h/mL) was significantly less ( p = 0.001) than that of IV aqueous solution (63.4 ± 3.00 ng.h/mL), which might explicate the drug availability in brain tissues rather than plasma [ 101 ]. The absolute bioavailability of the drug in plasma after IN in situ gel application was calculated to be 43.07%.…”

Development of an Icariin-Loaded Bilosome-Melittin Formulation with Improved Anticancer Activity against Cancerous Pancreatic Cells

“…As evidenced by the negative sign of X1, the particle size decreases significantly with increasing cholesterol:Span 20 ratio, i.e., higher proportion of cholesterol resulted in higher vesicular size. This could be attributed to the packing of cholesterol molecules between the surfactant alkyl chain, resulting in the higher size of the formed vesicles [30,31]. Additionally, it can be assumed that the increase in size with the increase in the concentration of MEL and bile salts could be attributed to the opposite charge attractions between these factors, with the possibility of integration within the geometrical structure of the formed vesicles.…”