Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice
Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (...
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MDPI AG
2024-01-01
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| author | Jawaher Abdullah Alamoudi Thanaa A. El-Masry Mohamed Nasr Ismail T. Ibrahim Hanaa A. Ibrahim Hebatallah M. Saad Maysa M. F. El-Nagar Samar Zuhair Alshawwa Amal Alrashidi Enas I. El Zahaby |
| author_facet | Jawaher Abdullah Alamoudi Thanaa A. El-Masry Mohamed Nasr Ismail T. Ibrahim Hanaa A. Ibrahim Hebatallah M. Saad Maysa M. F. El-Nagar Samar Zuhair Alshawwa Amal Alrashidi Enas I. El Zahaby |
| author_sort | Jawaher Abdullah Alamoudi |
| collection | DOAJ |
| description | Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs). Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m (<sup>99m</sup>Tc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice. Results: The prepared NCs improved ORL’s solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice. Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC. |
| first_indexed | 2024-03-08T10:38:14Z |
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| language | English |
| last_indexed | 2024-03-08T10:38:14Z |
| publishDate | 2024-01-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-361bf38e1ddd4a3f9078c1d55435b2372024-01-26T18:06:02ZengMDPI AGPharmaceuticals1424-82472024-01-011719610.3390/ph17010096Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in MiceJawaher Abdullah Alamoudi0Thanaa A. El-Masry1Mohamed Nasr2Ismail T. Ibrahim3Hanaa A. Ibrahim4Hebatallah M. Saad5Maysa M. F. El-Nagar6Samar Zuhair Alshawwa7Amal Alrashidi8Enas I. El Zahaby9Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35712, EgyptLabeled Compounds Department, Hot Laboratory Centre, Egyptian Atomic Energy Authority, Cairo 13759, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptDepartment of Pathology, Faculty of Veterinary Medicine, Matrouh University, Cairo 51511, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35712, EgyptBackground: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs). Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m (<sup>99m</sup>Tc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice. Results: The prepared NCs improved ORL’s solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice. Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC.https://www.mdpi.com/1424-8247/17/1/96bioavailabilitybiodistributionnanocrystalsliver damageorlistatradiolabeling |
| spellingShingle | Jawaher Abdullah Alamoudi Thanaa A. El-Masry Mohamed Nasr Ismail T. Ibrahim Hanaa A. Ibrahim Hebatallah M. Saad Maysa M. F. El-Nagar Samar Zuhair Alshawwa Amal Alrashidi Enas I. El Zahaby Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice Pharmaceuticals bioavailability biodistribution nanocrystals liver damage orlistat radiolabeling |
| title | Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice |
| title_full | Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice |
| title_fullStr | Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice |
| title_full_unstemmed | Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice |
| title_short | Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice |
| title_sort | fabrication of nanocrystals for enhanced distribution of a fatty acid synthase inhibitor orlistat as a promising method to relieve solid ehrlich carcinoma induced hepatic damage in mice |
| topic | bioavailability biodistribution nanocrystals liver damage orlistat radiolabeling |
| url | https://www.mdpi.com/1424-8247/17/1/96 |
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