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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.)

Skin cancer treatment effectiveness is improved by iontophoresis of EGFR-targeted liposomes containing 5-FU compared with subcutaneous injection

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Autor(es):
Petrilli, Raquel [1, 2] ; Eloy, Josimar O. [1, 2, 3] ; Saggioro, Fabiano P. [4] ; Chesca, Deise L. [4] ; de Souza, Marina Claro [2] ; Dias, Marcos V. S. [5] ; daSilva, Luis L. P. [5] ; Lee, Robert J. [1] ; Lopez, Renata F. V. [2]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 - USA
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Univ Fed Ceara, Sch Pharm Dent & Nursing, 1210 Capitao Francisco Pedro St, BR-60430372 Fortaleza, CE - Brazil
[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Ave Bandeirantes S-N, Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, BR-14049900 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF CONTROLLED RELEASE; v. 283, p. 151-162, AUG 10 2018.
Citações Web of Science: 5
Resumo

Squamous cell carcinoma (SCC) is a malignant tumor in which epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis and malignancy. For SCC treatment, cetuximab, an anti-EGFR antibody, is administered in combination with a chemotherapeutic drug for improved efficacy. In this work, an EGFR-targeted immunoliposome loaded with 5-fluorouracil (5-FU) was developed to allow co-administration of the antibody and the chemotherapeutic agent and selective delivery to SCC cells. Topically applied iontophoresis and subcutaneous injections of the 5-FU-loaded immunoliposomes were employed in an SCC xenograft animal model to evaluate the influence of the administration route on therapeutic efficacy. In vitro, cellular uptake of cetuximab-immunoliposomes by EGFR-positive SCC cells was 3.5-fold greater than the uptake of control liposomes. Skin penetration studies showed that iontophoresis of immunoliposomes doubled the 5-FU penetration into the viable epidermis compared with the same treatment with control liposomes. In vivo, subcutaneous injection of immunoliposomes reduced tumor volume by >60% compared with the negative control and approximately 50% compared with the 5-FU solution and control liposome treatments. Interestingly, topical administration via iontophoresis improved tumor reduction by almost 2-fold compared with subcutaneous administration of 5-FU solution and control liposomes but was equally effective for the immunoliposome treatment. However, histological analysis showed that iontophoresis of immunoliposomes was more effective than subcutaneous injection in reducing cell proliferation, resulting in cells with less aggressive characteristics. In conclusion, topical administration of immunoliposomes containing 5-FU using iontophoresis is a promising strategy for SCC treatment. (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