Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies
Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a p...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016424000343 |
| _version_ | 1797291746557689856 |
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| author | Mohammed F. Aldawsari Mohammad Azhar Kamal Mohamed F. Balaha Talha Jawaid Mohammed Jafar Sana Hashmi Majid Ahmad Ganaie Aftab Alam |
| author_facet | Mohammed F. Aldawsari Mohammad Azhar Kamal Mohamed F. Balaha Talha Jawaid Mohammed Jafar Sana Hashmi Majid Ahmad Ganaie Aftab Alam |
| author_sort | Mohammed F. Aldawsari |
| collection | DOAJ |
| description | Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer. |
| first_indexed | 2024-03-07T19:42:12Z |
| format | Article |
| id | doaj.art-12eae6e0ece3464289ba6fc28bc5f4b3 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-07T19:42:12Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-12eae6e0ece3464289ba6fc28bc5f4b32024-02-29T05:18:22ZengElsevierSaudi Pharmaceutical Journal1319-01642024-03-01323101984Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studiesMohammed F. Aldawsari0Mohammad Azhar Kamal1Mohamed F. Balaha2Talha Jawaid3Mohammed Jafar4Sana Hashmi5Majid Ahmad Ganaie6Aftab Alam7Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, EgyptDepartment of Pharmacology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi ArabiaDepartment of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi ArabiaDepartment of Pharmaceutics, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi ArabiaDepartment of Pharmacology & Toxicology, College of Dentistry and Pharmacy, Buraydah Colleges, 51418 Buraydah, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia; Corresponding author.Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.http://www.sciencedirect.com/science/article/pii/S1319016424000343RibociclibNanostructured Lipidic CarriersBoxBehnken DesignCLSMDermatokineticsSkin cancer |
| spellingShingle | Mohammed F. Aldawsari Mohammad Azhar Kamal Mohamed F. Balaha Talha Jawaid Mohammed Jafar Sana Hashmi Majid Ahmad Ganaie Aftab Alam Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies Saudi Pharmaceutical Journal Ribociclib Nanostructured Lipidic Carriers BoxBehnken Design CLSM Dermatokinetics Skin cancer |
| title | Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies |
| title_full | Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies |
| title_fullStr | Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies |
| title_full_unstemmed | Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies |
| title_short | Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies |
| title_sort | optimized ribociclib nanostructured lipid carrier for the amelioration of skin cancer inferences from ex vivo skin permeation and dermatokinetic studies |
| topic | Ribociclib Nanostructured Lipidic Carriers BoxBehnken Design CLSM Dermatokinetics Skin cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1319016424000343 |
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