In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance

Ahmed, Osama A. A.; Badr-Eldin, Shaimaa M.

doi:10.2147/ijn.s181587

Cited by 27 publications

(18 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The in situ gel formulation loaded with optimized FB niosomes exhibited appropriate viscosity of 117 ± 0.98 cps that permits facile instillation into the nose. After exposure to SNF, the formulation was converted from viscous solution into gel, as depicted by the increased gelling factor [ 30 ]. The viscosity of the formulation after gelation was increased to 435 ± 1.78 cps.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

“…A mean cumulative amount of FLB permeated through the mucosal surface per unit surface area (µg/cm 2 ) was plotted as a function of time. Then, permeation parameters, namely steady-state flux (J ss ; µg/cm 2 .h), permeability (P c ), and diffusion (D) coefficients were computed [ 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, the nanoscale size of the vesicles results in a great surface area, thus increased contact area with the mucosal epithelium and successively improving the chance of drug permeation [38]. Nanovesicles have been reported to have the potential to enhance drug absorption through the nasal membrane barrier and to demonstrate a high efficacy in enhancing drug bioavailability [40]. However, mucociliary clearance can help to reduce the contact time of drug-loaded nanovesicles on the mucosal surface inside the nose.…”

Section: Discussionmentioning

confidence: 99%

“…SNF was composed of sodium chloride (0.877%), calcium chloride (0.058% w/v), and potassium chloride (0.298% w/v) dissolved in deionized water [39]. Mucosa and gel samples were mounted between the two chambers and the donor chamber [40]. The area of the chamber of the utilized Franz automated diffusion cell (MicroettePlus; Hanson Research, Chatsworth, CA, USA) was 1.76 cm 2 .…”

Section: Optimized Flb Trf Gel Ex Vivo Permeation Studymentioning

confidence: 99%

RETRACTED: Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route

et al. 2020

Self Cite

View full text Add to dashboard Cite

Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.

show abstract

“…Nasal delivery has recently gained a great consideration as a highly vascular, convenient, and non-invasive route for drug delivery that is able to surpass the presystemic metabolism of many drugs. 7 In addition, the unique anatomy of the nasal cavity, which permits absorption via the olfactory trigeminal regions, could provide a route that surmounts the blood-brain barrier (BBB), and, thus, offers direct delivery of the drugs to the brain. 8 Previous researchers have evaluated and demonstrated the effectiveness of the nasal route for brain delivery of drugs.…”

Section: Introductionmentioning

confidence: 99%

<p>Optimized Nanostructured Lipid Carriers Integrated into In Situ Nasal Gel for Enhancing Brain Delivery of Flibanserin</p>

Fahmy¹,

Ahmed²,

Badr-Eldin³

et al. 2020

IJN

Self Cite

View full text Add to dashboard Cite

Background and Aim: Flibanserin (FLB) is a multifunctional serotonergic agent used for treating hypoactive sexual desire disorder in premenopausal women via oral administration. FLB has a reported limited oral bioavailability of 33% that could be attributed to the drug's first-pass metabolism. In addition, FLB has a pH-dependent solubility that could be a challenging factor for drug dissolution in the body neutral fluid, and consequently, absorption via mucosal barriers. Thus, this work aims at investigating the potential of utilizing nanostructured lipid carriers (NLCs) to overcome the aforementioned drawbacks and to enhance nose-to-brain drug delivery. Methods: Box-Behnken design was applied to explore the impact of solid lipid % (SL%, X 1), liquid lipid % (LL%, X 2), and sonication time (ST, X 3) on particle size. The optimized NLC formulation was characterized and incorporated into gellan gum in situ gel. The prepared gel was subjected to in vitro drug release, in vivo pharmacokinetic performance, and histopathological assessment in rats. Results: Statistical analysis revealed a significant negative effect for both SL% and ST on NLCs size. In contrast, a significant positive effect was observed for the LL%. The optimized formulation showed spherical shape with vesicular size of 114.63 nm. The optimized FLB-NLC in situ gel exhibited adequate stability and enhanced in vitro release compared to raw FLB control gel. The plasma and brain concentrations of the drug after nasal administration in rats increased by more than 3-6-fold, respectively, compared to raw FLB in situ gel. In addition, the histopathological studies revealed the absence of any pathological signs. Conclusion: The aforementioned results highlight the safety of FLB-NLC in situ nasal gel and its potential to improve the drug bioavailability and brain delivery.

show abstract

In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance

Cited by 27 publications

References 45 publications

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

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

RETRACTED: Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route

<p>Optimized Nanostructured Lipid Carriers Integrated into In Situ Nasal Gel for Enhancing Brain Delivery of Flibanserin</p>

Contact Info

Product

Resources

About