{"title":"用于增强甲氨蝶呤透皮给药的 Transethosomes 的配制、表征和优化","authors":"Priyanka J. Veer, Vinayak S. Mastiholimath","doi":"10.1007/s12247-023-09799-2","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Methotrexate (MTX) is an antineoplastic drug used in the treatment of rheumatoid arthritis (RA). Given that it is a class IV drug with low permeability and solubility, this study aims to improve MTX skin permeation by loading it in transethosomes (TEs) and casting a transethosomal patch that allows for dose quantification to mitigate toxicity.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To accomplish this goal, MTX transethosomes (TEs) were developed using the thin film hydration technique and optimized using the Box-Behnken design (BBD) with soya phosphatidylcholine 50, Tween 80, and ethanol as independent variables using the desirability function. Furthermore, zeta potential (ZP) analysis and high-resolution transmission electron microscopy (HR-TEM) were used to confirm the stability and surface morphology of TEs. A transdermal patch was also designed and evaluated from the optimized TE (OPTZ TEs) batch using a solvent casting method with hydroxypropyl methylcellulose (HPMC) as the polymer, dimethyl sulfoxide (DMSO) as a permeation enhancer, and polyethylene glycol (PEG 400) as the plasticizer. Furthermore, ex vivo skin permeation and deposition through rat skin proved that the TE patch had better drug permeation and retention within the skin layers.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The highest desirability batch had 92.19 ± 3.826 nm vesicle size, 0.35 ± 0.062 PDI, 74.05 ± 5.157% EE and 62.75 ± 4.448% Q8h which were within the predicted results. Furthermore, ZP was found to be more than − 30 mV, and HR-TEM results proved that the TE vesicles were spherical. The results of the evaluation parameters such as weight variation, folding endurance, and thickness were 0.07 ± 0.01 g, 82.3 ± 1.52 folds, and 0.93 ± 0.01, respectively, and were well within the limits. The TE patch incorporated more than 90% of the drug confirmed by the drug content analysis which allowed ex vivo permeation for almost 24 h providing a sustained release action with a permeation flux of 19 ± 1.08 and an enhancement ratio of 3.68 when compared to the MTX solution.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study suggests that MTX-loaded transethosomal patch not only enhanced the skin permeation but also provided a 24-h release profile and reduced its toxicity.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\n","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"29 1","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Formulation, Characterization, and Optimization of Transethosomes for Enhanced Transdermal Delivery of Methotrexate\",\"authors\":\"Priyanka J. Veer, Vinayak S. Mastiholimath\",\"doi\":\"10.1007/s12247-023-09799-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>Methotrexate (MTX) is an antineoplastic drug used in the treatment of rheumatoid arthritis (RA). Given that it is a class IV drug with low permeability and solubility, this study aims to improve MTX skin permeation by loading it in transethosomes (TEs) and casting a transethosomal patch that allows for dose quantification to mitigate toxicity.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>To accomplish this goal, MTX transethosomes (TEs) were developed using the thin film hydration technique and optimized using the Box-Behnken design (BBD) with soya phosphatidylcholine 50, Tween 80, and ethanol as independent variables using the desirability function. Furthermore, zeta potential (ZP) analysis and high-resolution transmission electron microscopy (HR-TEM) were used to confirm the stability and surface morphology of TEs. A transdermal patch was also designed and evaluated from the optimized TE (OPTZ TEs) batch using a solvent casting method with hydroxypropyl methylcellulose (HPMC) as the polymer, dimethyl sulfoxide (DMSO) as a permeation enhancer, and polyethylene glycol (PEG 400) as the plasticizer. Furthermore, ex vivo skin permeation and deposition through rat skin proved that the TE patch had better drug permeation and retention within the skin layers.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>The highest desirability batch had 92.19 ± 3.826 nm vesicle size, 0.35 ± 0.062 PDI, 74.05 ± 5.157% EE and 62.75 ± 4.448% Q8h which were within the predicted results. Furthermore, ZP was found to be more than − 30 mV, and HR-TEM results proved that the TE vesicles were spherical. The results of the evaluation parameters such as weight variation, folding endurance, and thickness were 0.07 ± 0.01 g, 82.3 ± 1.52 folds, and 0.93 ± 0.01, respectively, and were well within the limits. 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Formulation, Characterization, and Optimization of Transethosomes for Enhanced Transdermal Delivery of Methotrexate
Purpose
Methotrexate (MTX) is an antineoplastic drug used in the treatment of rheumatoid arthritis (RA). Given that it is a class IV drug with low permeability and solubility, this study aims to improve MTX skin permeation by loading it in transethosomes (TEs) and casting a transethosomal patch that allows for dose quantification to mitigate toxicity.
Methods
To accomplish this goal, MTX transethosomes (TEs) were developed using the thin film hydration technique and optimized using the Box-Behnken design (BBD) with soya phosphatidylcholine 50, Tween 80, and ethanol as independent variables using the desirability function. Furthermore, zeta potential (ZP) analysis and high-resolution transmission electron microscopy (HR-TEM) were used to confirm the stability and surface morphology of TEs. A transdermal patch was also designed and evaluated from the optimized TE (OPTZ TEs) batch using a solvent casting method with hydroxypropyl methylcellulose (HPMC) as the polymer, dimethyl sulfoxide (DMSO) as a permeation enhancer, and polyethylene glycol (PEG 400) as the plasticizer. Furthermore, ex vivo skin permeation and deposition through rat skin proved that the TE patch had better drug permeation and retention within the skin layers.
Results
The highest desirability batch had 92.19 ± 3.826 nm vesicle size, 0.35 ± 0.062 PDI, 74.05 ± 5.157% EE and 62.75 ± 4.448% Q8h which were within the predicted results. Furthermore, ZP was found to be more than − 30 mV, and HR-TEM results proved that the TE vesicles were spherical. The results of the evaluation parameters such as weight variation, folding endurance, and thickness were 0.07 ± 0.01 g, 82.3 ± 1.52 folds, and 0.93 ± 0.01, respectively, and were well within the limits. The TE patch incorporated more than 90% of the drug confirmed by the drug content analysis which allowed ex vivo permeation for almost 24 h providing a sustained release action with a permeation flux of 19 ± 1.08 and an enhancement ratio of 3.68 when compared to the MTX solution.
Conclusion
This study suggests that MTX-loaded transethosomal patch not only enhanced the skin permeation but also provided a 24-h release profile and reduced its toxicity.
期刊介绍:
The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories:
Materials science,
Product design,
Process design, optimization, automation and control,
Facilities; Information management,
Regulatory policy and strategy,
Supply chain developments ,
Education and professional development,
Journal of Pharmaceutical Innovation publishes four issues a year.