Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach
Albeit its established efficacy as an anti-hyperlipidemic agent, pitavastatin (PIT) has been shown to have other various therapeutic effects. One of these effects is the anti-cancer activity against hepatocellular carcinoma (HCC). This effect has been evaluated in this study for the first time via i...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2120925 |
| _version_ | 1811274323309101056 |
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| author | Maged Kharouba Amal El-Kamel Radwa Mehanna Eman Thabet Lamia Heikal |
| author_facet | Maged Kharouba Amal El-Kamel Radwa Mehanna Eman Thabet Lamia Heikal |
| author_sort | Maged Kharouba |
| collection | DOAJ |
| description | Albeit its established efficacy as an anti-hyperlipidemic agent, pitavastatin (PIT) has been shown to have other various therapeutic effects. One of these effects is the anti-cancer activity against hepatocellular carcinoma (HCC). This effect has been evaluated in this study for the first time via its oral delivery loaded in bilosomes both in vitro in hepatocellular carcinoma (HCC) cell line; HepG2 and in vivo in an Ehrlich ascites carcinoma (EAC) model. Moreover, the impact of surface modification of bilosomes with lactoferrin (LF) as an active targeting ligand for HCC was investigated. Bilosomes were prepared by thin-film hydration and different molar phospholipid to bile salt ratios were used to optimize the bilosomal formulation. The molar phospholipid to bile salt ratio was adjusted to 4:1 at pH 7.4. LF-coated bilosomes possessed a particle size, PDI, entrapment efficiency, and zeta potential of 112.28 nm ± 6.35, 0.229 ± 0.06, 90.56% ± 3.22, and −7.86 mV ± 1.13, respectively. LF-coated bilosomes also increased permeation of PIT when tested on Caco-2 cells by 3.1-folds (compared to uncoated ones or free PIT solution). It also improved the cytotoxicity of HepG2 spheroids 44-folds more than PIT-free solution. RT-PCR analysis showed that LF-coated PIT-loaded bilosomes caused an improvement (2-fold increase) in the apoptotic potential of PIT mediated by caspase-3. In conclusion, the optimized LF-coated PIT-loaded bilosomes were cytotoxic to HCC with improved hepatocytes permeation and cellular uptake. Thus, the proposed formula could be a promising treatment for HCC. |
| first_indexed | 2024-04-12T23:16:57Z |
| format | Article |
| id | doaj.art-274034ab9aea4dc4acd6a73017febb3d |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-12T23:16:57Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-274034ab9aea4dc4acd6a73017febb3d2022-12-22T03:12:39ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-012912925294410.1080/10717544.2022.2120925Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approachMaged Kharouba0Amal El-Kamel1Radwa Mehanna2Eman Thabet3Lamia Heikal4Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptMedical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptMedical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptAlbeit its established efficacy as an anti-hyperlipidemic agent, pitavastatin (PIT) has been shown to have other various therapeutic effects. One of these effects is the anti-cancer activity against hepatocellular carcinoma (HCC). This effect has been evaluated in this study for the first time via its oral delivery loaded in bilosomes both in vitro in hepatocellular carcinoma (HCC) cell line; HepG2 and in vivo in an Ehrlich ascites carcinoma (EAC) model. Moreover, the impact of surface modification of bilosomes with lactoferrin (LF) as an active targeting ligand for HCC was investigated. Bilosomes were prepared by thin-film hydration and different molar phospholipid to bile salt ratios were used to optimize the bilosomal formulation. The molar phospholipid to bile salt ratio was adjusted to 4:1 at pH 7.4. LF-coated bilosomes possessed a particle size, PDI, entrapment efficiency, and zeta potential of 112.28 nm ± 6.35, 0.229 ± 0.06, 90.56% ± 3.22, and −7.86 mV ± 1.13, respectively. LF-coated bilosomes also increased permeation of PIT when tested on Caco-2 cells by 3.1-folds (compared to uncoated ones or free PIT solution). It also improved the cytotoxicity of HepG2 spheroids 44-folds more than PIT-free solution. RT-PCR analysis showed that LF-coated PIT-loaded bilosomes caused an improvement (2-fold increase) in the apoptotic potential of PIT mediated by caspase-3. In conclusion, the optimized LF-coated PIT-loaded bilosomes were cytotoxic to HCC with improved hepatocytes permeation and cellular uptake. Thus, the proposed formula could be a promising treatment for HCC.https://www.tandfonline.com/doi/10.1080/10717544.2022.2120925Repurposingpitavastatinanti-cancerliver carcinomaHepG2Caco-2 |
| spellingShingle | Maged Kharouba Amal El-Kamel Radwa Mehanna Eman Thabet Lamia Heikal Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach Drug Delivery Repurposing pitavastatin anti-cancer liver carcinoma HepG2 Caco-2 |
| title | Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach |
| title_full | Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach |
| title_fullStr | Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach |
| title_full_unstemmed | Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach |
| title_short | Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach |
| title_sort | pitavastatin loaded bilosomes for oral treatment of hepatocellular carcinoma a repurposing approach |
| topic | Repurposing pitavastatin anti-cancer liver carcinoma HepG2 Caco-2 |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2120925 |
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