Development and Evaluation of Optimized Thiolated Chitosan Proniosomal Gel Containing Duloxetine for Intranasal Delivery

Khatoon, Maryam; Sohail, Muhammad; Shahnaz, Gul; Rehman, Fiza Ur; Din, Fakhar ud; Rehman, Asim Ur; Ullah, Naseem; Amin, Umair; Khan, Gul Majid; Shah, Kifayat Ullah

doi:10.1208/s12249-019-1484-y

Cited by 35 publications

(21 citation statements)

References 46 publications

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“…In a previous study, it was reported that the extent of DLX release at pH 7.4 after 24 h from the prepared proniosomal gel and mucoadhesive proniosomal gel was 30% and 24%, respectively. 19 This showed that our DLX cubo-gels could provide better-controlled release profiles and greater DLX extents compared to the formulations in the previous studies. Polynomial analysis, fitted with a 2-factor interaction model, was used to illustrate the release data at Q6.…”

Section: Dovepressmentioning

confidence: 63%

“…46 In a previous study, it was stated that increasing Tween 80 concentration increased the EE% of DLX in the prepared proniosomes due to the increased drug wettability. 19 In another study, it was reported that increasing the Tween 80 concentration increased the EE% of risperidone due to the formation of a coating layer over the prepared cubosomes, which retain additional drug amount. 22 In vitro DLX Release…”

Section: Dovepressmentioning

confidence: 97%

“…13 In a previous study, the PS of proniosomes prepared by Khatoon et al for brain targeting of DLX ranged from 166 to 842 nm. 19 The smallest size belonged to F4 prepared using 0.1 lipid ratio, 20% w/v PF127 and 5% w/v PF68. The linear model was the model of choice for the PS.…”

Section: Characterization Of the Prepared In Situ Cubo-gels Ps Pdi mentioning

confidence: 98%

“…22 In another study, Khatoon et al reported that increasing Tween 80 concentration led to a reduction in PS of DLX proniosomes due to the decrease in surface tension. 19 GMO is an amphiphilic polar lipid. At concentration above CMC, it forms micelles.…”

Section: Characterization Of the Prepared In Situ Cubo-gels Ps Pdi mentioning

confidence: 99%

“…18 In another study, Khatoon et al evaluated the intranasal administration of thiolated chitosan gel containing DLX proniosomes to improve its brain delivery. 19 This study aims to formulate and characterize DLX in situ cubosomal gel to improve its bioavailability and enhance its brain targeting. A three-factor, three-level CCD was used to study the effects of different variables on the studied responses to prepare an optimized formulation.…”

Section: Introductionmentioning

confidence: 99%

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<p>Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies</p>

Elsenosy¹,

Abdelbary²,

Elshafeey³

et al. 2020

IJN

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Purpose: Duloxetine (DLX) is dual serotonin and norepinephrine reuptake inhibitor suffering from limited bioavailability (≈ 40%) due to extensive hepatic metabolism. This work aims to formulate and evaluate DLX intranasal thermoreversible cubosomal gels to enhance its bioavailability and ensure efficient brain targeting. Materials and Methods: Cubo-gels were prepared by 3 3 central composite design with three independent factors, lipid ratio (glycerol monooleate: glycerol tripalmitate), Pluronic F127%, and Pluronic F68%. The prepared formulations were evaluated for their particle size (PS), gelling temperature (GT), entrapment efficiency (EE%), and in vitro release. The cubogel with the highest desirability (0.88) was chosen as the optimized formulation. DLX cubogel was evaluated using differential scanning calorimetry, Fourier-transform infrared spectroscopy, X-ray powder diffraction, and transmission electron microscopy. Cytotoxicity study, ex vivo permeation study and in vivo bio-distribution study were conducted to evaluate the safety and efficacy of brain targeting. Results: The optimum cubo-gel was composed of 3.76 lipid ratio, 20% w/v PF127, and 5% w/v PF68. It had PS of 265.13 ± 9.85 nm, GT of 32 ± 0.05°C, EE% of 98.13 ± 0.50%, and showed controlled release behavior where 33% DLX was released within 6 hrs. The plain in situ cubo-gel had a significantly higher IC 50 compared to DLX solution and DLX-loaded in situ cubo-gel. The ex vivo permeation study showed 1.27 enhancement in the drug permeation from DLX in situ cubo-gel. According to the in vivo bio-distribution study in plasma and brain, the intranasal DLX in situ cubo-gel showed a 1.96 fold improvement in brain bioavailability compared to the intranasal solution. Its BTE% and DTP% were 137.77 and 10.5, respectively, indicating efficient brain targeting after intranasal administration. Conclusion: Accordingly, intranasal DLX in situ cubo-gel can be considered as an innovative nano-carrier delivery system for bioavailability enhancement and efficient brain targeting of DLX to maximize its effect.

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Section: Dovepressmentioning

confidence: 63%