Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management
Background/Objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB’s low solubility, poor bioavailability, resistance, poor targeting, and...
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2024-12-01
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| author | Maha M. Ghalwash Amr Gamal Fouad Nada H. Mohammed Marwa M. Nagib Sherif Faysal Abdelfattah Khalil Amany Belal Samar F. Miski Nisreen Khalid Aref Albezrah Amani Elsayed Ahmed H. E. Hassan Eun Joo Roh Shaimaa El-Housiny |
| author_facet | Maha M. Ghalwash Amr Gamal Fouad Nada H. Mohammed Marwa M. Nagib Sherif Faysal Abdelfattah Khalil Amany Belal Samar F. Miski Nisreen Khalid Aref Albezrah Amani Elsayed Ahmed H. E. Hassan Eun Joo Roh Shaimaa El-Housiny |
| author_sort | Maha M. Ghalwash |
| collection | DOAJ |
| description | Background/Objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB’s low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally. This investigation set out to design an intratumoral in situ pH-sensitive hydrogel of SDB-invasomes (IPHS-INV) that can effectively treat BCSC by improving SDB’s bioavailability, sustainability, targeting, and efficacy while also reducing its resistance and undesirable side effects. Methods: Numerous S-INV formulations were developed using Box–Behnken Design Expert and tested before settling on the optimum S-INV formulation. An experimental 7, 12-dimethylbenzanthracene (DMBA) carcinoma rat model was used for in vivo studies of the IPHS-INV formulation after it was combined with chitosan. Results: Phospholipids (1.72% <i>w</i>/<i>w</i>), cholesterol (0.15% <i>w</i>/<i>w</i>), ethanol (1% <i>v</i>/<i>v</i>), and cineole (1.5% <i>v</i>/<i>v</i>) were shown to be the optimal components in the SDB-invasome formulation. The IPHS-INV formulation outperformed the permeation and bioavailability of free SDB by 7.14 and 6 times, respectively, and sustained its release by 57.41%. The IPHS-INV formulation showed a decrease in tumor volume of 99.05% and a reduction of hypercellular tumors, indicating its anti-cancer activity. The intratumoral IPHS-INV formulation maintained a higher concentration of SDB in tumors, indicating its targeting activity. Conclusions: These findings support the use of the intratumoral IPHS-INV formulation as an effective strategy for the treatment of BCSC. |
| format | Article |
| id | doaj-art-0f600069b17e45ebb5a48f52868f96f5 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-0f600069b17e45ebb5a48f52868f96f52025-01-24T13:45:05ZengMDPI AGPharmaceuticals1424-82472024-12-011813110.3390/ph18010031Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer ManagementMaha M. Ghalwash0Amr Gamal Fouad1Nada H. Mohammed2Marwa M. Nagib3Sherif Faysal Abdelfattah Khalil4Amany Belal5Samar F. Miski6Nisreen Khalid Aref Albezrah7Amani Elsayed8Ahmed H. E. Hassan9Eun Joo Roh10Shaimaa El-Housiny11Department of Pharmaceutics and Drug Manufacturing, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11435, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Deraya University, Minya 61768, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo 11435, EgyptPharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif 21944, Saudi ArabiaPharmacology and Toxicology Department, College of Pharmacy, Taibah University, Madina 42278, Saudi ArabiaDepartment of Obstetric & Gynecology, College of Medicine, Taif University, Taif 21944, Saudi ArabiaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Taif University, Taif 21944, Saudi ArabiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptChemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaDepartment of Pharmaceutics and Drug Manufacturing, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo 11435, EgyptBackground/Objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB’s low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally. This investigation set out to design an intratumoral in situ pH-sensitive hydrogel of SDB-invasomes (IPHS-INV) that can effectively treat BCSC by improving SDB’s bioavailability, sustainability, targeting, and efficacy while also reducing its resistance and undesirable side effects. Methods: Numerous S-INV formulations were developed using Box–Behnken Design Expert and tested before settling on the optimum S-INV formulation. An experimental 7, 12-dimethylbenzanthracene (DMBA) carcinoma rat model was used for in vivo studies of the IPHS-INV formulation after it was combined with chitosan. Results: Phospholipids (1.72% <i>w</i>/<i>w</i>), cholesterol (0.15% <i>w</i>/<i>w</i>), ethanol (1% <i>v</i>/<i>v</i>), and cineole (1.5% <i>v</i>/<i>v</i>) were shown to be the optimal components in the SDB-invasome formulation. The IPHS-INV formulation outperformed the permeation and bioavailability of free SDB by 7.14 and 6 times, respectively, and sustained its release by 57.41%. The IPHS-INV formulation showed a decrease in tumor volume of 99.05% and a reduction of hypercellular tumors, indicating its anti-cancer activity. The intratumoral IPHS-INV formulation maintained a higher concentration of SDB in tumors, indicating its targeting activity. Conclusions: These findings support the use of the intratumoral IPHS-INV formulation as an effective strategy for the treatment of BCSC.https://www.mdpi.com/1424-8247/18/1/31basal cell skin cancersonidegibinvasomeschitosanbioavailabilitytargeting |
| spellingShingle | Maha M. Ghalwash Amr Gamal Fouad Nada H. Mohammed Marwa M. Nagib Sherif Faysal Abdelfattah Khalil Amany Belal Samar F. Miski Nisreen Khalid Aref Albezrah Amani Elsayed Ahmed H. E. Hassan Eun Joo Roh Shaimaa El-Housiny Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management Pharmaceuticals basal cell skin cancer sonidegib invasomes chitosan bioavailability targeting |
| title | Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management |
| title_full | Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management |
| title_fullStr | Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management |
| title_full_unstemmed | Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management |
| title_short | Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib–Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management |
| title_sort | fabrication and in vivo evaluation of in situ ph sensitive hydrogel of sonidegib invasomes via intratumoral delivery for basal cell skin cancer management |
| topic | basal cell skin cancer sonidegib invasomes chitosan bioavailability targeting |
| url | https://www.mdpi.com/1424-8247/18/1/31 |
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