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Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study
The present study aimed to prepare, characterize, and evaluate a thermo-responsive sol–gel for intranasal delivery of lamotrigine (LTG), which was designed for sustained drug delivery to treat epilepsy. LTG sol–gel was prepared using the cold method by changing the concentrations of poloxamer 407 an...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606094/ https://www.ncbi.nlm.nih.gov/pubmed/37888390 http://dx.doi.org/10.3390/gels9100817 |
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author | Riaz, Maria Zaman, Muhammad Hameed, Huma Sarwar, Hafiz Shoaib Khan, Mahtab Ahmad Irfan, Ali Shazly, Gamal A. Paiva-Santos, Ana Cláudia Jardan, Yousef A. Bin |
author_facet | Riaz, Maria Zaman, Muhammad Hameed, Huma Sarwar, Hafiz Shoaib Khan, Mahtab Ahmad Irfan, Ali Shazly, Gamal A. Paiva-Santos, Ana Cláudia Jardan, Yousef A. Bin |
author_sort | Riaz, Maria |
collection | PubMed |
description | The present study aimed to prepare, characterize, and evaluate a thermo-responsive sol–gel for intranasal delivery of lamotrigine (LTG), which was designed for sustained drug delivery to treat epilepsy. LTG sol–gel was prepared using the cold method by changing the concentrations of poloxamer 407 and poloxamer 188, which were used as thermo-reversible polymers. The optimized formulations of sol–gel were analyzed for clarity, pH, viscosity, gelation temperature, gelation time, spreadability, drug content, in vitro drug release studies, ex vivo permeation studies, and in vivo toxicological studies. FTIR, XRD, and DSC were performed to determine the thermal stability of the drug and polymers. The prepared formulations had a clear appearance in sol form; they were liquid at room temperature and became gel at temperatures between 31 °C and 36 °C. The pH was within the range of the nasal pH, between 6.2 and 6.4. The drug content was found to be between 92% and 94%. In vitro drug release studies indicated that the formulations released up to 92% of the drug within 24 h. The FTIR, DSC, and XRD analyses showed no interaction between the drug and the polymer. A short-term stability study indicated that the formulation was stable at room temperature and at 4–8 °C. There was a slight increase in viscosity at room temperature, which may be due to the evaporation of the vehicle. A histological study indicated that there were no signs of toxicity seen in vital organs, such as the brain, kidney, liver, heart, and spleen. It can be concluded from the above results that the prepared intranasal sol–gel for the delivery of LTG is safe for direct nose-to-brain delivery to overcome the first-pass effect and thus enhance bioavailability. It can be considered an effective alternative to conventional drug delivery for the treatment of epilepsy. |
format | Online Article Text |
id | pubmed-10606094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106060942023-10-28 Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study Riaz, Maria Zaman, Muhammad Hameed, Huma Sarwar, Hafiz Shoaib Khan, Mahtab Ahmad Irfan, Ali Shazly, Gamal A. Paiva-Santos, Ana Cláudia Jardan, Yousef A. Bin Gels Article The present study aimed to prepare, characterize, and evaluate a thermo-responsive sol–gel for intranasal delivery of lamotrigine (LTG), which was designed for sustained drug delivery to treat epilepsy. LTG sol–gel was prepared using the cold method by changing the concentrations of poloxamer 407 and poloxamer 188, which were used as thermo-reversible polymers. The optimized formulations of sol–gel were analyzed for clarity, pH, viscosity, gelation temperature, gelation time, spreadability, drug content, in vitro drug release studies, ex vivo permeation studies, and in vivo toxicological studies. FTIR, XRD, and DSC were performed to determine the thermal stability of the drug and polymers. The prepared formulations had a clear appearance in sol form; they were liquid at room temperature and became gel at temperatures between 31 °C and 36 °C. The pH was within the range of the nasal pH, between 6.2 and 6.4. The drug content was found to be between 92% and 94%. In vitro drug release studies indicated that the formulations released up to 92% of the drug within 24 h. The FTIR, DSC, and XRD analyses showed no interaction between the drug and the polymer. A short-term stability study indicated that the formulation was stable at room temperature and at 4–8 °C. There was a slight increase in viscosity at room temperature, which may be due to the evaporation of the vehicle. A histological study indicated that there were no signs of toxicity seen in vital organs, such as the brain, kidney, liver, heart, and spleen. It can be concluded from the above results that the prepared intranasal sol–gel for the delivery of LTG is safe for direct nose-to-brain delivery to overcome the first-pass effect and thus enhance bioavailability. It can be considered an effective alternative to conventional drug delivery for the treatment of epilepsy. MDPI 2023-10-14 /pmc/articles/PMC10606094/ /pubmed/37888390 http://dx.doi.org/10.3390/gels9100817 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Riaz, Maria Zaman, Muhammad Hameed, Huma Sarwar, Hafiz Shoaib Khan, Mahtab Ahmad Irfan, Ali Shazly, Gamal A. Paiva-Santos, Ana Cláudia Jardan, Yousef A. Bin Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study |
title | Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study |
title_full | Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study |
title_fullStr | Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study |
title_full_unstemmed | Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study |
title_short | Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study |
title_sort | lamotrigine-loaded poloxamer-based thermo-responsive sol–gel: formulation, in vitro assessment, ex vivo permeation, and toxicology study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606094/ https://www.ncbi.nlm.nih.gov/pubmed/37888390 http://dx.doi.org/10.3390/gels9100817 |
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