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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Cetuximab Immunoliposomes Enhance Delivery of 5-FU to Skin Squamous Carcinoma Cells

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Petrilli, Raquel ; Eloy, Josimar O. ; Lopez, Renata F. V. ; Lee, Robert J.
Total Authors: 4
Document type: Journal article
Source: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 17, n. 2, p. 301-308, 2017.
Web of Science Citations: 7

Background: Topical chemotherapy of skin cancers is a promising strategy for reduction of side effects and for improvement of patient compliance. The combination of the chemotherapeutic 5-fluouracil (5-FU) and the antiEGFR antibody cetuximab is a strategy to inhibit tumor growth. Their skin penetration, however, is hampered by their high hydrophilicity, which could be improved by encapsulation in delivery systems. Furthermore, it is a challenge to encapsulate hydrophilic drugs. The conjugation of an antibody to a liposome, maintaining its activity, is also a difficult task. Objective: Thus, we aimed to develop 5-FU liposomes and cetuximab-conjugated liposomes (immunoliposomes) of 5-FU to improve drug cytotoxicity against skin cancer cells. Method: We characterized them by particle size, zeta potential, loading efficiency and antibody integrity. To optimize the loading efficiency of 5-FU, a series of liposomes were prepared, using different methods and drug-to-lipid ratios. Results: Liposomes containing DSPC and Chol at drug-to-lipid ratio 0.1 prepared by the thin lipid hydration method resulted in the best 5-FU encapsulation and were chosen to conjugate with cetuximab. Cetuximab was directly coupled to preformed liposomes using DSPE-mPEG2000-Mal as an anchor. In A431 skin carcinoma cells, at 72 h, 5-FU liposomes showed a 5-fold lower IC50 than 5-FU solution. Additionally, 5-FU immunoliposomes resulted in a 4-fold lower cetuximab IC50 than cetuximab solution, demonstrating synergism with a combination index lower than 1 and potential to improve 5-FU and cetuximab cytotoxicity. Conclusion: Liposomes and immunoliposomes containing 5-FU were developed and cetuximab remained active as demonstrated in cell culture studies. (AU)

FAPESP's process: 12/23764-3 - Topical application of liposomes containing cetuximab: the effect of physical skin penetration enhancement techniques for cutaneous squamous cell carcinoma
Grantee:Raquel Petrilli
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/15134-2 - Preparation of immunoliposomes for topical skin cancer treatment
Grantee:Raquel Petrilli
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 14/22451-7 - Sustained drug delivery systems targeting the epithelial tissue
Grantee:Renata Fonseca Vianna Lopez
Support type: Research Projects - Thematic Grants