Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy

Abstract The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays with iontophoresis (MN-IP), electroporation (MN-EP) in conjunction with applying photodynamic therapy (PDT), sonodynamic...

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Main Authors: Samir Ali Abd El-Kaream, Nabila Gaber Ali Hussein, Sohier Mahmoud El-Kholey, Ahmed Mohammed Abd Elmoez Ibrahim Elhelbawy
Format: Article
Language:English
Published: Nature Portfolio 2024-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-58033-7
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author Samir Ali Abd El-Kaream
Nabila Gaber Ali Hussein
Sohier Mahmoud El-Kholey
Ahmed Mohammed Abd Elmoez Ibrahim Elhelbawy
author_facet Samir Ali Abd El-Kaream
Nabila Gaber Ali Hussein
Sohier Mahmoud El-Kholey
Ahmed Mohammed Abd Elmoez Ibrahim Elhelbawy
author_sort Samir Ali Abd El-Kaream
collection DOAJ
description Abstract The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays with iontophoresis (MN-IP), electroporation (MN-EP) in conjunction with applying photodynamic therapy (PDT), sonodynamic therapy (SDT) and sono-photodynamic therapy (SPDT) as an up-to-date activated cancer treatment modality. Study was conducted on 120 male Swiss Albino mice, inoculated with Ehrlich ascites carcinoma (EAC) divided into 9 groups. We employed three different arrays of MN electrodes were used (parallel, triangular, and circular), EP, IP with different volts (6, 9, 12 V), an infrared laser and an ultrasound (pulsed and continuous wave) as our two energy sources. Results revealed that parallel 6 V TDD@MN@IP@EP can be used as effective delivery system for G. macrophyllus from skin directly to target EAC cells. In addition MN@IP@EP@TDD G. macrophyllus is a potential SPS for SPDT treatment of EAC. With respect to normal control mice and as opposed to the EAC untreated control mice, MN@EP@IP TDD G. macrophyllus in the laser, ultrasound, and combination activated groups showed a significant increase in the antioxidant markers TAC level and the GST, GR, Catalase, and SOD activities, while decrease in lipid peroxidation oxidative stress parameter MDA levels. In addition significantly increased apoptotic genes expressions (p53, caspase (3, 9), Bax, and TNF alpha) and on the other hand decreased anti- apoptotic (Bcl-2) and angiogenic (VEGF) genes expressions. Moreover significantly ameliorate liver and kidney function decreasing ALT, AST, urea and creatinine respectively. Furthermore MN@IP@EP@TDD G. macrophyllus combined with SPDT was very effective at reducing the growth of tumors and even causing cell death according to microscopic H&E stain results. This process may be related to a sono- and/or photochemical activation mechanism. According to the findings, MN@IP@EP@TDD G. macrophyllus has a lot of potential as a novel, efficient delivery method that in combination with infrared laser and ultrasound activation SPDT demonstrated promising anticancer impact for treating cancer.
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spelling doaj.art-c74369f44c5d45a8b051087f5fd0c6c42024-04-07T11:19:14ZengNature PortfolioScientific Reports2045-23222024-04-0114111510.1038/s41598-024-58033-7Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapySamir Ali Abd El-Kaream0Nabila Gaber Ali Hussein1Sohier Mahmoud El-Kholey2Ahmed Mohammed Abd Elmoez Ibrahim Elhelbawy3Applied Medical Chemistry Department, Affiliated Medical Research Institute, Alexandria UniversityApplied Medical Chemistry Department, Affiliated Medical Research Institute, Alexandria UniversityMedical Biophysics Department, Affiliated Medical Research Institute, Alexandria UniversityApplied Medical Chemistry Department, Affiliated Medical Research Institute, Alexandria UniversityAbstract The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays with iontophoresis (MN-IP), electroporation (MN-EP) in conjunction with applying photodynamic therapy (PDT), sonodynamic therapy (SDT) and sono-photodynamic therapy (SPDT) as an up-to-date activated cancer treatment modality. Study was conducted on 120 male Swiss Albino mice, inoculated with Ehrlich ascites carcinoma (EAC) divided into 9 groups. We employed three different arrays of MN electrodes were used (parallel, triangular, and circular), EP, IP with different volts (6, 9, 12 V), an infrared laser and an ultrasound (pulsed and continuous wave) as our two energy sources. Results revealed that parallel 6 V TDD@MN@IP@EP can be used as effective delivery system for G. macrophyllus from skin directly to target EAC cells. In addition MN@IP@EP@TDD G. macrophyllus is a potential SPS for SPDT treatment of EAC. With respect to normal control mice and as opposed to the EAC untreated control mice, MN@EP@IP TDD G. macrophyllus in the laser, ultrasound, and combination activated groups showed a significant increase in the antioxidant markers TAC level and the GST, GR, Catalase, and SOD activities, while decrease in lipid peroxidation oxidative stress parameter MDA levels. In addition significantly increased apoptotic genes expressions (p53, caspase (3, 9), Bax, and TNF alpha) and on the other hand decreased anti- apoptotic (Bcl-2) and angiogenic (VEGF) genes expressions. Moreover significantly ameliorate liver and kidney function decreasing ALT, AST, urea and creatinine respectively. Furthermore MN@IP@EP@TDD G. macrophyllus combined with SPDT was very effective at reducing the growth of tumors and even causing cell death according to microscopic H&E stain results. This process may be related to a sono- and/or photochemical activation mechanism. According to the findings, MN@IP@EP@TDD G. macrophyllus has a lot of potential as a novel, efficient delivery method that in combination with infrared laser and ultrasound activation SPDT demonstrated promising anticancer impact for treating cancer.https://doi.org/10.1038/s41598-024-58033-7
spellingShingle Samir Ali Abd El-Kaream
Nabila Gaber Ali Hussein
Sohier Mahmoud El-Kholey
Ahmed Mohammed Abd Elmoez Ibrahim Elhelbawy
Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
Scientific Reports
title Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
title_full Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
title_fullStr Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
title_full_unstemmed Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
title_short Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
title_sort microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy
url https://doi.org/10.1038/s41598-024-58033-7
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