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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Petrilli, Raquel ; Eloy, Josimar O. ; Lopez, Renata F. V. ; Lee, Robert J.
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 17, n. 2, p. 301-308, 2017.
Citações Web of Science: 7
Resumo

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)

Processo FAPESP: 12/23764-3 - Aplicação tópica de lipossomas contendo cetuximabe: efeito do uso de métodos físicos de penetração cutânea no carcinoma celular escamoso de pele
Beneficiário:Raquel Petrilli
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/15134-2 - Preparo de imunolipossomas para o tratamento tópico de câncer de pele
Beneficiário:Raquel Petrilli
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 14/22451-7 - Sistemas de liberação sustentada e direcionada de fármacos para o tecido epitelial
Beneficiário:Renata Fonseca Vianna Lopez
Linha de fomento: Auxílio à Pesquisa - Temático