Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury

Purpose: The repositioning of previously approved drugs is occupying the researchers’ plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive t...

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Main Authors: Nermin M. Sheta, Amira A. El-Gazar, Ghada M. Ragab, Marwa A. Essa, Khaled M. Abdel-Haleem, Rania Moataz El-Dahmy
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2024-07-01
Series:Advanced Pharmaceutical Bulletin
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Online Access:https://apb.tbzmed.ac.ir/PDF/apb-14-346.pdf
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author Nermin M. Sheta
Amira A. El-Gazar
Ghada M. Ragab
Marwa A. Essa
Khaled M. Abdel-Haleem
Rania Moataz El-Dahmy
author_facet Nermin M. Sheta
Amira A. El-Gazar
Ghada M. Ragab
Marwa A. Essa
Khaled M. Abdel-Haleem
Rania Moataz El-Dahmy
author_sort Nermin M. Sheta
collection DOAJ
description Purpose: The repositioning of previously approved drugs is occupying the researchers’ plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics. Methods: A (23 ) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An in-vivo experiment was done to test the prepared formula’s efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid B (GABAB), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor kappa B (NF-κB) p65, malondialdehyde (MDA), superoxide dismutase (SOD), and histopathology. Results: The particle size (PS) and entrapment efficiency percent (EE%) speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. In vitro release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability=1, with 630.09±3.53 µg/cm2 of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABAB and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity. Conclusion: Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.
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spelling doaj-art-0f4c77c06f034be288d62ce75e2436da2025-08-20T02:04:11ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082024-07-0114234636310.34172/apb.2024.031apb-42164Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain InjuryNermin M. Sheta0Amira A. El-Gazar1Ghada M. Ragab2Marwa A. Essa3Khaled M. Abdel-Haleem4Rania Moataz El-Dahmy5Pharmaceutics Department, Faculty of Pharmacy, October 6 University, Giza, Egypt.Pharmacology and Toxicology Department, Faculty of Pharmacy, October 6 University, Giza, Egypt.Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr University for Science & Technology (MUST), Giza, Egypt.Biochemistry Department, Faculty of Pharmacy, October 6 University, Giza, Egypt.Pharmaceutics Department, Faculty of Pharmacy, October 6 University, Giza, Egypt.Pharmaceutics Department, Faculty of Pharmacy, October 6 University, Giza, Egypt.Purpose: The repositioning of previously approved drugs is occupying the researchers’ plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics. Methods: A (23 ) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An in-vivo experiment was done to test the prepared formula’s efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid B (GABAB), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor kappa B (NF-κB) p65, malondialdehyde (MDA), superoxide dismutase (SOD), and histopathology. Results: The particle size (PS) and entrapment efficiency percent (EE%) speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. In vitro release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability=1, with 630.09±3.53 µg/cm2 of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABAB and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity. Conclusion: Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.https://apb.tbzmed.ac.ir/PDF/apb-14-346.pdfbaclofenfakgababnanoparticlestransdermaltraumatic brain injury
spellingShingle Nermin M. Sheta
Amira A. El-Gazar
Ghada M. Ragab
Marwa A. Essa
Khaled M. Abdel-Haleem
Rania Moataz El-Dahmy
Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury
Advanced Pharmaceutical Bulletin
baclofen
fak
gabab
nanoparticles
transdermal
traumatic brain injury
title Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury
title_full Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury
title_fullStr Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury
title_full_unstemmed Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury
title_short Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury
title_sort transcending traditional treatment the therapeutical potential of nanovesicles for transdermal baclofen delivery in repeated traumatic brain injury
topic baclofen
fak
gabab
nanoparticles
transdermal
traumatic brain injury
url https://apb.tbzmed.ac.ir/PDF/apb-14-346.pdf
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