Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells
Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancemen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2403 |
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| author | Vancha Harish Devesh Tewari Sharfuddin Mohd Pilli Govindaiah Malakapogu Ravindra Babu Rajesh Kumar Monica Gulati Kuppusamy Gowthamarajan SubbaRao V. Madhunapantula Dinesh Kumar Chellappan Gaurav Gupta Kamal Dua Siva Dallavalasa Sachin Kumar Singh |
| author_facet | Vancha Harish Devesh Tewari Sharfuddin Mohd Pilli Govindaiah Malakapogu Ravindra Babu Rajesh Kumar Monica Gulati Kuppusamy Gowthamarajan SubbaRao V. Madhunapantula Dinesh Kumar Chellappan Gaurav Gupta Kamal Dua Siva Dallavalasa Sachin Kumar Singh |
| author_sort | Vancha Harish |
| collection | DOAJ |
| description | Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in C<sub>max</sub> (1.07-folds), AUC<sub>0-t</sub> (4.70-folds), t<sub>1/2</sub> (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells. |
| first_indexed | 2024-03-09T18:45:07Z |
| format | Article |
| id | doaj.art-7fecb91f7f1c4bcc996cd550416dea03 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:45:07Z |
| publishDate | 2022-11-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-7fecb91f7f1c4bcc996cd550416dea032023-11-24T06:21:42ZengMDPI AGPharmaceutics1999-49232022-11-011411240310.3390/pharmaceutics14112403Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 CellsVancha Harish0Devesh Tewari1Sharfuddin Mohd2Pilli Govindaiah3Malakapogu Ravindra Babu4Rajesh Kumar5Monica Gulati6Kuppusamy Gowthamarajan7SubbaRao V. Madhunapantula8Dinesh Kumar Chellappan9Gaurav Gupta10Kamal Dua11Siva Dallavalasa12Sachin Kumar Singh13School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, IndiaDepartment of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, IndiaSchool of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, IndiaDepartment of Pathology, School of Medicine, Wayne State University, Detroit, MI 48202, USASchool of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, IndiaSchool of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, IndiaSchool of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, IndiaDepartment of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty 643001, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine Laboratory (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research, Bannimantapa, Sri Shivarathreeshwara Nagar, Mysore 570015, IndiaSchool of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, MalaysiaSchool of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jaipur 302017, IndiaFaculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, AustraliaCenter of Excellence in Molecular Biology and Regenerative Medicine Laboratory (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research, Bannimantapa, Sri Shivarathreeshwara Nagar, Mysore 570015, IndiaSchool of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, IndiaMany natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in C<sub>max</sub> (1.07-folds), AUC<sub>0-t</sub> (4.70-folds), t<sub>1/2</sub> (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.https://www.mdpi.com/1999-4923/14/11/2403Box–Behnken Designoral bioavailabilitydrug releasesolid lipid nanoparticlesXanthohumol |
| spellingShingle | Vancha Harish Devesh Tewari Sharfuddin Mohd Pilli Govindaiah Malakapogu Ravindra Babu Rajesh Kumar Monica Gulati Kuppusamy Gowthamarajan SubbaRao V. Madhunapantula Dinesh Kumar Chellappan Gaurav Gupta Kamal Dua Siva Dallavalasa Sachin Kumar Singh Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells Pharmaceutics Box–Behnken Design oral bioavailability drug release solid lipid nanoparticles Xanthohumol |
| title | Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells |
| title_full | Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells |
| title_fullStr | Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells |
| title_full_unstemmed | Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells |
| title_short | Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells |
| title_sort | quality by design based formulation of xanthohumol loaded solid lipid nanoparticles with improved bioavailability and anticancer effect against pc 3 cells |
| topic | Box–Behnken Design oral bioavailability drug release solid lipid nanoparticles Xanthohumol |
| url | https://www.mdpi.com/1999-4923/14/11/2403 |
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