- Title
- In vitro and in vivo toxicity and biodistribution of paclitaxel-loaded cubosomes as a drug delivery nanocarrier : a case study using an A431 skin cancer xenograft model
- Creator
- Zhai, Jiali; Tan, Fiona; Luwor, Rodney; Srinivasa Reddy, T.; Ahmed, Nuzhat; Drummond, Calum; Tran, Nhiem
- Date
- 2020
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/173787
- Identifier
- vital:14750
- Identifier
-
https://doi.org/10.1021/acsabm.0c00269
- Identifier
- ISBN:2576-6422 (ISSN)
- Abstract
- Cubosomes with an internal three-dimensional (3D) periodic and porous particulate nanostructure have emerged as a promising drug delivery system for hydrophobic small molecules as well as large biomolecules over the past several decades. Limited understanding of their safety profiles and biodistribution, however, hinders clinical translation. This study used monoolein-based cubosomes stabilized by Pluronic F127 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)] polymers to encapsulate paclitaxel (PTX) as a model drug and investigated the in vitro cytotoxicity, in vivo acute response, and whole body biodistribution of the developed nanoparticles. Comparison of the PTX and nanoparticle cytotoxicity in two-dimensional and 3D spheroid cell models revealed distinct differences, with the cells in the 3D model found to be more tolerable to unloaded PTX as well as the PTX-loaded nanoparticle form. One-time intraperitoneal (i.p.) injection of unloaded cubosomes were generally well tolerated up to 400 mg/kg. Using the A431 skin cancer xenograft model, in vivo imaging studies showed the preferential accumulation of PTX-loaded cubosomes at the tumor sites following i.p. injection. Lastly, average tumor size was reduced by approximately 50% in the nanoparticle-based treatment group compared to the unloaded PTX drug group. The study provides significant information on the biological response of cubosomes and highlights their potential as a versatile drug delivery platform for safe and effective delivery of chemotherapeutic drugs. © 2020 American Chemical Society.; The authors acknowledge the Capability Development Fund Scheme of RMIT University, the Maxwell Eagle Endowment Award and the CASS Foundation Science/Medicine Grant for financial support. N.T. is a recipient of an RMIT Vice-Chancellor’s Research Fellowship.
- Publisher
- American Chemical Society
- Relation
- ACS Applied Bio Materials Vol. 3, no. 7 (2020), p. 4198-4207
- Rights
- Copyright © 2020 American Chemical Society
- Rights
- This metadata is freely available under a CCO license
- Subject
- 03 Chemical Sciences; 09 Engineering; 3D cell viability; A431 xenograft; biodistribution; cubosome; drug delivery; paclitaxel
- Reviewed
- Funder
- The authors acknowledge the Capability Development Fund Scheme of RMIT University, the Maxwell Eagle Endowment Award and the CASS Foundation Science/Medicine Grant for financial support. N.T. is a recipient of an RMIT Vice-Chancellor’s Research Fellowship.
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