RETRACTED: Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation

Abstract

Flibanserin (FLB) is a multifunctional serotonergic agent that was recently approved by the FDA for the oral treatment of premenopausal women with hypoactive sexual desire disorder. FLB is a centrally acting drug that has a low oral bioavailability of 33% owing to its exposure to the hepatic first-pass effect, as well as its pH-dependent solubility, which could be an obstacle hindering the drug dissolution and absorption via mucosal barriers. Thus, this work aimed at overcoming the aforementioned drawbacks and promoting the nose-to-brain delivery of FLB via the formulation of an intra-nasal in situ niosomal gel. The Box–Behnken design was employed to study the impact of Span® 85 concentration (X1), hydration time (X2), and pH of the hydrating buffer (X3) on the vesicle size and drug entrapment. The optimized formulation exhibited a spherical shape with a vesicular size of 46.35 nm and entrapment efficiency of 92.48%. The optimized FLB niosomes integrated into gellan gum-based in situ gel exhibited enhanced ex vivo permeation and improved plasma and brain concentrations after nasal administration in rats compared to raw FLB. These findings highlight the capability of the proposed intra-nasal FLB niosomal in situ gel to boost the drug bioavailability and to promote its direct delivery to the brain.

RETRACTED: Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells

“…Free-TQ had been taken by passive transport, while phytosomes had been taken by endocytosis. In addition, phytosomes containing abundant phospholipids could carry amphiphilic agents to cross the cell membrane resulting in high intracellular drug concentrations [ 36 , 37 , 38 ]. However, the optimized formula showed relatively-weak cytotoxic activity against EA.hy926 non-cancerous endothelial cells.…”

Piceatannol-Loaded Bilosome-Stabilized Zein Protein Exhibits Enhanced Cytostatic and Apoptotic Activities in Lung Cancer Cells

“…The random distribution of the points within the limits in both the externally studentized residuals vs. predicted response and the residual vs. run plots indicated that neither constant error nor lurking variable that can influence the measured particle size existed. Additionally, the highly linear pattern displayed in the predicted versus actual globule size plot reflected good coincidence between the observed and anticipated values [ 55 , 56 ]. Regarding the measured particle size, the comparatively low calculated standard deviation indicated homogenous and uniform distribution of the formulated bilosomal dispersions.…”

Formulation and Optimization of Avanafil Biodegradable Polymeric Nanoparticles: A Single-Dose Clinical Pharmacokinetic Evaluation

“…The human pharmacokinetic study of AVA showed a lower initial plasma concentration than that of NPs, possibly due to the slow solubilization rate of raw AVA. After 1.5 h, the plasma concentration for raw AVA was lower than for PLGA NPs, due to the rapid metabolism and elimination of free AVA compared to the encapsulated AVA within the PLGA NPs [ 50 , 51 ]. The findings also revealed that optimized AVA-PLGA NPs significantly changed the pharmacokinetic profile, and improved the bioavailability of AVA by > 1.3 times than that of the raw AVA.…”