Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor
Purpose: The ultimate goal of this study is to develop a novel delivery system for a new potent cytotoxic compound, CCI-001, with anti-b tubulin activity, so that the drug can be effectively administered and at the same time its harmful side effects can be reduced. Methods: In the current study, CCI...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-07-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31877 |
| _version_ | 1827162507713708032 |
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| author | Alessandra Spada Jaber Emami Foroughalsadat Sanaee Maral Aminpour Igor, M Paiva Jack Tuszynski Afsaneh Lavasanifar |
| author_facet | Alessandra Spada Jaber Emami Foroughalsadat Sanaee Maral Aminpour Igor, M Paiva Jack Tuszynski Afsaneh Lavasanifar |
| author_sort | Alessandra Spada |
| collection | DOAJ |
| description | Purpose: The ultimate goal of this study is to develop a novel delivery system for a new potent cytotoxic compound, CCI-001, with anti-b tubulin activity, so that the drug can be effectively administered and at the same time its harmful side effects can be reduced. Methods: In the current study, CCI-001 was loaded into serum albumin (SA), using a modified desolvation method, generating CCI-001-SA nanoparticles. Both bovine and human SA were used for the encapsulation of this drug candidate. Optimum conditions for drug loading were achieved when already formed and crosslinked albumin nanoparticles were incubated overnight at 37°C with CCI-001 solutions. The CCI-001-loaded albumin nanoparticles were assessed for average particle diameter and polydispersity, zeta potential, drug loading, in vitro release, morphology and cell toxicity against SW620 and HCT116 colorectal cancer cells. Results: The spherical nanoparticles obtained were negatively charged (~ -30 mV) and had an average diameter of ~ 130 nm, with a narrow size distribution. The in vitro release of CCI-001 from the albumin nanoparticles showed a sustained release pattern over 24 hours without any initial burst release, compared to the fast release of the free drug under experimental conditions. No difference between the SA from the two species in terms of CCI-001 loading was observed. However, a significant difference was observed between the release profiles of CCI-001 from drug-loaded HSA and drug-loaded BSA nanoparticles with HSA nanoparticles showing slower drug release (mean release time, MRT, values of 5.14 ± 0.33 h and 6.88 ± 0.15 h for BSA-NPs and HSA-NPs, respectively, P < 0.01). Cellular toxicity studies showed higher cytotoxicity for CCI-001-SA compared to the free drug (IC50s of 0.62 ± 0.31 nM vs 2.06 ± 0.29 nM in SW620 cells and 0.9 ± 0.1 nM vs 4.2 ± 0.2 nM in HCT116 cells, for CCI-001-HSA NPs and free drug, respectively). Therefore, despite the low drug content level in the HSA nanoparticles of CCI-001, the formulation provides relevant concentrations for further in vivo studies in animal models due to high drug potency. Conclusions: The data support the potential use of albumin as a nanocarrier for CCI-001 in biological systems. |
| first_indexed | 2024-03-12T08:41:21Z |
| format | Article |
| id | doaj.art-e9e859ff08a3446c9eec50e87e871211 |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2025-03-21T00:45:55Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-e9e859ff08a3446c9eec50e87e8712112024-08-03T05:57:41ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262021-07-0124310.18433/jpps31877Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitorAlessandra Spada0Jaber Emami1Foroughalsadat Sanaee2Maral Aminpour3Igor, M Paiva4Jack Tuszynski5Afsaneh Lavasanifar6Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada, and DIMEAS, Politecnico di Torino, Turin, Italy Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, and School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AlbertaFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AlbertaDepartment of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada, and DIMEAS, Politecnico di Torino, Turin, Italy University of Alberta, Edmonton, AB CanadaPurpose: The ultimate goal of this study is to develop a novel delivery system for a new potent cytotoxic compound, CCI-001, with anti-b tubulin activity, so that the drug can be effectively administered and at the same time its harmful side effects can be reduced. Methods: In the current study, CCI-001 was loaded into serum albumin (SA), using a modified desolvation method, generating CCI-001-SA nanoparticles. Both bovine and human SA were used for the encapsulation of this drug candidate. Optimum conditions for drug loading were achieved when already formed and crosslinked albumin nanoparticles were incubated overnight at 37°C with CCI-001 solutions. The CCI-001-loaded albumin nanoparticles were assessed for average particle diameter and polydispersity, zeta potential, drug loading, in vitro release, morphology and cell toxicity against SW620 and HCT116 colorectal cancer cells. Results: The spherical nanoparticles obtained were negatively charged (~ -30 mV) and had an average diameter of ~ 130 nm, with a narrow size distribution. The in vitro release of CCI-001 from the albumin nanoparticles showed a sustained release pattern over 24 hours without any initial burst release, compared to the fast release of the free drug under experimental conditions. No difference between the SA from the two species in terms of CCI-001 loading was observed. However, a significant difference was observed between the release profiles of CCI-001 from drug-loaded HSA and drug-loaded BSA nanoparticles with HSA nanoparticles showing slower drug release (mean release time, MRT, values of 5.14 ± 0.33 h and 6.88 ± 0.15 h for BSA-NPs and HSA-NPs, respectively, P < 0.01). Cellular toxicity studies showed higher cytotoxicity for CCI-001-SA compared to the free drug (IC50s of 0.62 ± 0.31 nM vs 2.06 ± 0.29 nM in SW620 cells and 0.9 ± 0.1 nM vs 4.2 ± 0.2 nM in HCT116 cells, for CCI-001-HSA NPs and free drug, respectively). Therefore, despite the low drug content level in the HSA nanoparticles of CCI-001, the formulation provides relevant concentrations for further in vivo studies in animal models due to high drug potency. Conclusions: The data support the potential use of albumin as a nanocarrier for CCI-001 in biological systems.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31877 |
| spellingShingle | Alessandra Spada Jaber Emami Foroughalsadat Sanaee Maral Aminpour Igor, M Paiva Jack Tuszynski Afsaneh Lavasanifar Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor Journal of Pharmacy & Pharmaceutical Sciences |
| title | Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor |
| title_full | Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor |
| title_fullStr | Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor |
| title_full_unstemmed | Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor |
| title_short | Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor |
| title_sort | design and evaluation of albumin nanoparticles for the delivery of a novel β tubulin polymerization inhibitor |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31877 |
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