Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation
Background/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aime...
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2024-11-01
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| author | Hanan O. Farouk Marwa M. Nagib Amr Gamal Fouad Demiana M. Naguib Sherif Faysal Abdelfattah Khalil Amany Belal Samar F. Miski Nisreen Khalid Aref Albezrah Shatha Hallal Al-Ziyadi Gi-Hui Kim Ahmed H. E. Hassan Kyung-Tae Lee Doaa S. Hamad |
| author_facet | Hanan O. Farouk Marwa M. Nagib Amr Gamal Fouad Demiana M. Naguib Sherif Faysal Abdelfattah Khalil Amany Belal Samar F. Miski Nisreen Khalid Aref Albezrah Shatha Hallal Al-Ziyadi Gi-Hui Kim Ahmed H. E. Hassan Kyung-Tae Lee Doaa S. Hamad |
| author_sort | Hanan O. Farouk |
| collection | DOAJ |
| description | Background/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aimed to create an intra-tumoral in situ pH-responsive formulation of RLF–invasome (IPHRLI) for breast cancer treatment, with the goals of sustaining RLF release, minimizing adverse effects, and enhancing solubility, bioavailability, targeting, and effectiveness. Methods: Numerous RLF–invasome formulations were optimized using design expert software (version 12.0.6.0, StatEase Inc., Minneapolis, MN, USA). Integrating an optimal formulation with an amalgam of chitosan and glyceryl monooleate resulted in the IPHRLI formulation. In vivo testing of the IPHRLI formulation was conducted utilizing the Ehrlich cancer model. Results: Requirements for an optimum RLF–invasome formulation were met by a mixture of phospholipids (2.46%), ethanol (2.84%), and cineole (0.5%). The IPHRLI formulation substantially sustained its release by 75.41% after 8 h relative to free RLF. The bioavailability of intra-tumoral IPHRLI was substantially raised by 4.07-fold compared to oral free RLF. Histopathological and tumor volume analyses of intra-tumoral IPHRLI confirmed its efficacy and targeting effect. Conclusions: the intra-tumoral administration of the IPHRLI formulation may provide a potential strategy for breast cancer management. |
| format | Article |
| id | doaj-art-b05e1cbfa67946f3953c02017b5cd4f5 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-b05e1cbfa67946f3953c02017b5cd4f52024-11-26T18:17:28ZengMDPI AGPharmaceuticals1424-82472024-11-011711151810.3390/ph17111518Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo EvaluationHanan O. Farouk0Marwa M. Nagib1Amr Gamal Fouad2Demiana M. Naguib3Sherif Faysal Abdelfattah Khalil4Amany Belal5Samar F. Miski6Nisreen Khalid Aref Albezrah7Shatha Hallal Al-Ziyadi8Gi-Hui Kim9Ahmed H. E. Hassan10Kyung-Tae Lee11Doaa S. Hamad12Department of Pharmaceutics, Faculty of Pharmacy, Nahda University, Beni-Suef 62511, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo 11435, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Nahda University, Beni-Suef 62511, 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, Medina 42278, Saudi ArabiaDepartment of Obstetric & Gynecology, College of Medicine, Taif University, Taif 21944, Saudi ArabiaDepartment of Obstetric & Gynecology, College of Medicine, Taif University, Taif 21944, Saudi ArabiaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Nile Valley University, Fayoum 63518, EgyptBackground/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aimed to create an intra-tumoral in situ pH-responsive formulation of RLF–invasome (IPHRLI) for breast cancer treatment, with the goals of sustaining RLF release, minimizing adverse effects, and enhancing solubility, bioavailability, targeting, and effectiveness. Methods: Numerous RLF–invasome formulations were optimized using design expert software (version 12.0.6.0, StatEase Inc., Minneapolis, MN, USA). Integrating an optimal formulation with an amalgam of chitosan and glyceryl monooleate resulted in the IPHRLI formulation. In vivo testing of the IPHRLI formulation was conducted utilizing the Ehrlich cancer model. Results: Requirements for an optimum RLF–invasome formulation were met by a mixture of phospholipids (2.46%), ethanol (2.84%), and cineole (0.5%). The IPHRLI formulation substantially sustained its release by 75.41% after 8 h relative to free RLF. The bioavailability of intra-tumoral IPHRLI was substantially raised by 4.07-fold compared to oral free RLF. Histopathological and tumor volume analyses of intra-tumoral IPHRLI confirmed its efficacy and targeting effect. Conclusions: the intra-tumoral administration of the IPHRLI formulation may provide a potential strategy for breast cancer management.https://www.mdpi.com/1424-8247/17/11/1518breast cancerraloxifeneinvasomesbioavailabilitychitosantargeting |
| spellingShingle | Hanan O. Farouk Marwa M. Nagib Amr Gamal Fouad Demiana M. Naguib Sherif Faysal Abdelfattah Khalil Amany Belal Samar F. Miski Nisreen Khalid Aref Albezrah Shatha Hallal Al-Ziyadi Gi-Hui Kim Ahmed H. E. Hassan Kyung-Tae Lee Doaa S. Hamad Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation Pharmaceuticals breast cancer raloxifene invasomes bioavailability chitosan targeting |
| title | Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation |
| title_full | Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation |
| title_fullStr | Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation |
| title_full_unstemmed | Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation |
| title_short | Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation |
| title_sort | fabrication of an in situ ph responsive raloxifene loaded invasome hydrogel for breast cancer management in vitro and in vivo evaluation |
| topic | breast cancer raloxifene invasomes bioavailability chitosan targeting |
| url | https://www.mdpi.com/1424-8247/17/11/1518 |
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