Wu, Shibo;
(2024)
Development of novel topical formulations of 5-fluorouracil for treatment of skin cancer and actinic keratosis.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Wu_10195271_thesis_sig_removed.pdf Download (13MB) | Preview |
Abstract
This study explores improved topical formulations of 5-fluorouracil (5-FU) combined with berberine chloride for enhanced skin cancer and actinic keratosis treatment. 5-FU is a standard therapy for these conditions, but its effectiveness is hindered by systemic toxicity, resistance, and suboptimal pharmacokinetics. Our objective was to develop formulations optimizing 5-FU delivery to, rather than through, the skin, enhancing treatment efficacy while minimizing side effects and resistance. / Methodology: Our approach utilized in vitro assays and RNA sequencing to assess cell cytotoxicity and understand the molecular effects of 5-FU and berberine chloride. The synergy of these compounds was evaluated through their impact on cancer cell viability, inflammation, and drug resistance. Pre-formulation studies assessed 5-FU solubility and skin permeation, aiming for high drug retention and minimal systemic absorption. / Results: The study found that 5-FU and berberine chloride exhibited a strong synergistic effect in reducing cancer cell viability, notably lowering IC50 values. RNA sequencing revealed significant gene expression modulation, highlighting the downregulation of inflammation markers and upregulation of apoptosis pathways. Formulation efforts identified propylene glycol/Transcutol (PG/TC) binary systems as superior for 5-FU delivery, further enhanced by isopropyl myristate (IPM) to improve skin retention. The novel Carbopol® ETD 2020 gel formulation demonstrated promising results, outperforming conventional treatments in permeation efficiency and skin retention of 5-FU. / Conclusion: This investigation underscores the potential of combining 5-FU with berberine chloride in novel topical formulations to combat skin cancer and actinic keratosis. By enhancing drug delivery and efficacy while reducing adverse effects and resistance, these findings contribute significantly to the field of dermatological oncology treatment.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of novel topical formulations of 5-fluorouracil for treatment of skin cancer and actinic keratosis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10195271 |
Archive Staff Only
 |
View Item |
