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

Abstract

Rasagiline mesylate (RSM) is a hydrophilic drug with poor oral bioavailability (36%) because of hepatic first-pass metabolism. The present study focuses on delivering RSM directly to the brain through its inclusion within transferosomal in situ gel administered through the intranasal (IN) route. Transferosomes were formed by the thin-film hydration method with the aid of Design-Expert® software by varying the edge activator (EA) type in the absence or presence of cholesterol. By desirability calculations, the optimum formulation was composed of phosphatidylcholine and sodium deoxycholate as an EA (5:1%w/w) with no cholesterol. The optimum formulation was 198.63 ± 34.98 nm in size and displayed an entrapment efficiency of 95.73 ± 0.09%. Transmission electron microscopy revealed discrete and spherical vesicles. Optimized transferosomes were further incorporated into an in situ gel composed of 0.5% pectin, 15% Pluronic® F-127, and 5% Pluronic® F-68 and tested for the in vivo performance. The systemic as well as brain kinetics were assessed in rats by comparing the IN-administered in situ gel to the IV aqueous solution. The optimum in situ gel showed safety and biocompatibility on rats’ nasal mucosa with enhanced brain bioavailability (131.17%). Drug targeting efficiency and direct transport percentage indices (304.53% and 67.16%, respectively) supported successful brain targeting offering direct nose-to-brain drug delivery.

Cross-Linked Alginate Dialdehyde/Chitosan Hydrogel Encompassing Curcumin-Loaded Bilosomes for Enhanced Wound Healing Activity

“…The mean PS of the bilosomal formulations ranged from 197.10 ± 24.60 (F1) to 680.45 ± 9.65 nm (F8), as presented in Table 1 . The obtained nano-sized particles might be attributed to the use of anionic bile salts (SDC or SC), where the steric repulsion between the charged moieties of the negatively charged bile salts arranged on the surface of the bilosomal vesicles caused an increase in the curvature of the vesicles’ membrane, resulting in the formation of nanosized particles [ 64 ]. Statistical analysis of the investigated independent variables (A, B, and C) showed their significant effect on PS ( p < 0.01).…”

“…By testing the type of bile salt effect on EE% values (Factor A), it was noticed that the calculated curcumin EE% upon using SDC, which ranged from 92.50 ± 0.14 to 97.75 ± 0.10%, was significantly higher ( p < 0.01) when compared with SC formulations (ranged from 89.50 ± 0.07 to 85.20 ± 0.07%), as presented in Table 1 and Supplementary File (Figure S4a) . This associated significant increase in curcumin EE% when using SDC might be ascribed to its smaller molecular size (414.6 g/mol) and hence less steric hindrance upon closure of the particles [ 64 , 76 ]. In addition, SDC increased the EE% because it can be incorporated into the bilayer membrane surface, and it increased the flexibility of the lipid membrane and, consequently, increased the solubility of the drug in the lipid membrane, leading to an increased drug entrapment efficiency [ 77 , 78 ].…”

Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations

“… 150 , 152 El Shagea et al encapsulated rasagiline within transfersomes (RAS-T) and distributed them into a temperature-sensitive ISG (RAS-T-ISG; Pluronic ® F-127 based and pectin supported) for the treatment of Parkinson’s disease. 132 In the context of in-vitro release patterns, the burst drug release observed in RAS-T was significantly alleviated in RAS-T-ISG, which was attributable to the increased viscosity during the sol-gel transition. Following intranasal administration of RAS-T-ISG, notably elevated brain levels were evident compared to the intravenous administration of the free drug solution, and this was accompanied by lower drug concentrations in the plasma.…”

“… The ISG-NP (IN) showed a DTE of 304.53% and a DTP of 67.16%, confirming excellent brain delivery efficiency by the N2B route. [ 132 ] Resveratrol (AD) Lecithin, Cremophor RH 40, and ethanol Poloxamer 407 and Carbopol 934 Before PS 83.79 nm and EE 72.58% Tem. The ISG-NP (IN) presented 2.15 and 22.5 times higher Cmax and AUC than the drug suspension (PO).…”

Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2

“… 38 According to previously published research, intranasal application of various medications loaded into transferosomes increases their bioavailability. 39 , 40 …”