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Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers
BACKGROUND: The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer. METHODS: HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle s...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127833/ https://www.ncbi.nlm.nih.gov/pubmed/34012260 http://dx.doi.org/10.2147/IJN.S299443 |
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author | Yu, Guo Ali, Zakir Sajjad Khan, Anam Ullah, Kalim Jamshaid, Humzah Zeb, Alam Imran, Muhammad Sarwar, Sadia Choi, Han-Gon ud Din, Fakhar |
author_facet | Yu, Guo Ali, Zakir Sajjad Khan, Anam Ullah, Kalim Jamshaid, Humzah Zeb, Alam Imran, Muhammad Sarwar, Sadia Choi, Han-Gon ud Din, Fakhar |
author_sort | Yu, Guo |
collection | PubMed |
description | BACKGROUND: The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer. METHODS: HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo. RESULTS: The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced (P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs. CONCLUSION: These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC. |
format | Online Article Text |
id | pubmed-8127833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-81278332021-05-18 Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers Yu, Guo Ali, Zakir Sajjad Khan, Anam Ullah, Kalim Jamshaid, Humzah Zeb, Alam Imran, Muhammad Sarwar, Sadia Choi, Han-Gon ud Din, Fakhar Int J Nanomedicine Original Research BACKGROUND: The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer. METHODS: HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo. RESULTS: The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced (P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs. CONCLUSION: These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC. Dove 2021-05-11 /pmc/articles/PMC8127833/ /pubmed/34012260 http://dx.doi.org/10.2147/IJN.S299443 Text en © 2021 Yu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Yu, Guo Ali, Zakir Sajjad Khan, Anam Ullah, Kalim Jamshaid, Humzah Zeb, Alam Imran, Muhammad Sarwar, Sadia Choi, Han-Gon ud Din, Fakhar Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers |
title | Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers |
title_full | Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers |
title_fullStr | Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers |
title_full_unstemmed | Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers |
title_short | Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers |
title_sort | preparation, pharmacokinetics, and antitumor potential of miltefosine-loaded nanostructured lipid carriers |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127833/ https://www.ncbi.nlm.nih.gov/pubmed/34012260 http://dx.doi.org/10.2147/IJN.S299443 |
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