Thesis
Development of tumour-targeted delivery systems entrapping plumbagin for cancer therapy
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2019
- Thesis identifier
- T15224
- Person Identifier (Local)
- 201586325
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Plumbagin, a naphthoquinone mainly extracted from Plumbaginaceae plants, has been shown to have promising anti-cancer properties. However, its therapeutic potential is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use is further limited by its poor aqueous solubility and its rapid elimination in vivo. To overcome this limitation, we hypothesised that the entrapment of plumbagin within a delivery system conjugated to transferrin, whose receptors are overexpressed on many cancer cells, would result in a selective delivery to tumours after intravenous administration and a subsequently enhanced therapeutic efficacy. The aim of this study was to prepare and characterise transferrin-targeted delivery systems entrapping plumbagin. In this work, we demonstrated that plumbagin could be formulated in transferrin-bearing liposomes, PLGA-PEG nanoparticles and lipid-polymer hybrid nanoparticles. The entrapment of plumbagin in these tumour-targeted nanomedicines led to an increase in plumbagin uptake by cancer cells, and improved its anti-proliferative and apoptosis activity in B16-F10, A431 and T98G cell lines compared to that observed with the drug solution. The intravenous injection of transferrin-bearing lipid-polymer hybrid nanoparticles entrapping plumbagin led to the complete tumour suppression for 40% of B16-F10 tumours. In addition, the intravenous treatment of B16-F10 tumours with transferrin-bearing liposomes and polymeric nanoparticles led to 10% tumour suppression. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any visible signs of toxicity. In conclusion, plumbagin entrapped in these transferrin-bearing nanomedicines are therefore highly promising therapeutic systems that should be further optimised as therapeutic tools for cancer treatment.
- Advisor / supervisor
- Dufès, Christine
- Resource Type
- Note
- This thesis was previously held under moratorium from 22 August 2019 until 22 August 2024.
- DOI
- Date Created
- 2019
- Former identifier
- 9912724190302996
Relações
Itens
| Miniatura | Título | Data de carga | Acesso | Ações |
|---|---|---|---|---|
|
|
PDF of thesis T15224 | 2021-07-02 | Público | Baixar |