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

Fatma Mohamed Elsenosy,1 Ghada Ahmed Abdelbary,2 Ahmed Hassen Elshafeey,2 Ibrahim Elsayed,2,3 Ahmed Roshdy Fares2 1Department of Clinical Pharmacy, Children’s Cancer Hospital, Cairo57357, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Ca...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elsenosy FM, Abdelbary GA, Elshafeey AH, Elsayed I, Fares AR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	duloxetine central composite design cubosomes thermoreversible in situ gel intranasal brain targeting. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c638da08951e43af9373cbe923348ecc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c638da08951e43af9373cbe923348ecc
record_format	dspace
spelling	oai:doaj.org-article:c638da08951e43af9373cbe923348ecc2021-12-02T13:41:59ZBrain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies1178-2013https://doaj.org/article/c638da08951e43af9373cbe923348ecc2020-11-01T00:00:00Zhttps://www.dovepress.com/brain-targeting-of-duloxetine-hcl-via-intranasal-delivery-of-loaded-cu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fatma Mohamed Elsenosy,1 Ghada Ahmed Abdelbary,2 Ahmed Hassen Elshafeey,2 Ibrahim Elsayed,2,3 Ahmed Roshdy Fares2 1Department of Clinical Pharmacy, Children’s Cancer Hospital, Cairo57357, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ahmed Roshdy FaresDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El Aini Street, Cairo 11562, EgyptTel +20 12 88285866Email ahmed.roshdy@pharma.cu.edu.egPurpose: 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 33 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 cubo-gel with the highest desirability (0.88) was chosen as the optimized formulation. DLX cubo-gel 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 IC50 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.Keywords: duloxetine, central composite design, cubosomes, thermoreversible in situ gel, intranasal, brain targetingElsenosy FMAbdelbary GAElshafeey AHElsayed IFares ARDove Medical Pressarticleduloxetinecentral composite designcubosomesthermoreversible in situ gelintranasalbrain targeting.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 9517-9537 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	duloxetine central composite design cubosomes thermoreversible in situ gel intranasal brain targeting. Medicine (General) R5-920
spellingShingle	duloxetine central composite design cubosomes thermoreversible in situ gel intranasal brain targeting. Medicine (General) R5-920 Elsenosy FM Abdelbary GA Elshafeey AH Elsayed I Fares AR Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies
description	Fatma Mohamed Elsenosy,1 Ghada Ahmed Abdelbary,2 Ahmed Hassen Elshafeey,2 Ibrahim Elsayed,2,3 Ahmed Roshdy Fares2 1Department of Clinical Pharmacy, Children’s Cancer Hospital, Cairo57357, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ahmed Roshdy FaresDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El Aini Street, Cairo 11562, EgyptTel +20 12 88285866Email ahmed.roshdy@pharma.cu.edu.egPurpose: 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 33 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 cubo-gel with the highest desirability (0.88) was chosen as the optimized formulation. DLX cubo-gel 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 IC50 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.Keywords: duloxetine, central composite design, cubosomes, thermoreversible in situ gel, intranasal, brain targeting
format	article
author	Elsenosy FM Abdelbary GA Elshafeey AH Elsayed I Fares AR
author_facet	Elsenosy FM Abdelbary GA Elshafeey AH Elsayed I Fares AR
author_sort	Elsenosy FM
title	Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies
title_short	Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies
title_full	Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies
title_fullStr	Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies
title_full_unstemmed	Brain Targeting of Duloxetine HCL via Intranasal Delivery of Loaded Cubosomal Gel: In vitro Characterization, ex vivo Permeation, and in vivo Biodistribution Studies
title_sort	brain targeting of duloxetine hcl via intranasal delivery of loaded cubosomal gel: in vitro characterization, ex vivo permeation, and in vivo biodistribution studies
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/c638da08951e43af9373cbe923348ecc
work_keys_str_mv	AT elsenosyfm braintargetingofduloxetinehclviaintranasaldeliveryofloadedcubosomalgelinvitrocharacterizationexvivopermeationandinvivobiodistributionstudies AT abdelbaryga braintargetingofduloxetinehclviaintranasaldeliveryofloadedcubosomalgelinvitrocharacterizationexvivopermeationandinvivobiodistributionstudies AT elshafeeyah braintargetingofduloxetinehclviaintranasaldeliveryofloadedcubosomalgelinvitrocharacterizationexvivopermeationandinvivobiodistributionstudies AT elsayedi braintargetingofduloxetinehclviaintranasaldeliveryofloadedcubosomalgelinvitrocharacterizationexvivopermeationandinvivobiodistributionstudies AT faresar braintargetingofduloxetinehclviaintranasaldeliveryofloadedcubosomalgelinvitrocharacterizationexvivopermeationandinvivobiodistributionstudies
_version_	1718392580500094976

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

Ejemplares similares