Rethinking Breast Cancer Chemoprevention: Technological Advantages and Enhanced Performance of a Nanoethosomal-Based Hydrogel for Topical Administration of Fenretinide

Autor(es)

Apolinario, Alexsandra Conceicao ; Salata, Giovanna Cassone ; de Souza, Marcelo Medina ; Chorilli, Marlus ; Lopes, Luciana Biagini

• Tipo de documento: Artigo Científico
• Fonte: AAPS PHARMSCITECH; v. 23, n. 4, p. 14-pg., 2022-04-05.

Resumo

Herein, we developed an ethosomal hydrogel based on three types of ethosomes: simple, mixed (surfactant-based micelles and lipid vesicles) or binary (comprising two type of alcohols). Ethanol injection was employed for vesicles preparation, and sodium alginate, as gelling agent. We purposed the local-transdermal administration of the off-the-shelf retinoid fenretinide (FENR) for chemoprevention of breast cancer. Rheograms and flow index values for alginate dispersion (without ethosomes) and hydrogels containing simple, mixed or binary ethosomes suggested pseudoplastic behavior. An increase in the apparent viscosity was observed upon ethosome incorporation. The ethosomal hydrogel displayed increased bioadhesion compared to the alginate dispersion, suggesting that the lipid vesicles contribute to the gelling and bioadhesion processes. In the Hen's Egg Test-Chorioallantoic Membrane model, few spots of lysis and hemorrhage were observed for formulations containing simple (score of 2) and mixed vesicles (score 4), but not for the hydrogel based on the binary system, indicating its lower irritation potential. The binary ethosomal hydrogel provided a slower FENR in vitro release and delivered 2.6-fold less drug into viable skin layers compared to the ethosome dispersion, supporting the ability of the gel matrix to slow down drug release. The ethosomal hydrogel decreased by similar to five-fold the IC50 values of FENR in MCF-7 cells. In conclusion, binary ethosomal gels presented technological advantages, provided sustained drug release and skin penetration, and did not preclude drug cytotoxic effects, supporting their potential applicability as topical chemopreventive systems. (AU)

• Processo FAPESP: 18/13877-1 - Nanocarreadores para a quimioprevenção e tratamento localizado de tumores de mama
• Beneficiário: Luciana Biagini Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/13139-0 - Centro de Excelência na Descoberta de Novos Alvos
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 18/14375-0 - Sistemas nanoestruturados para veiculação tópica do retinoide sintético fenretinida visando a quimioprevenção do câncer de mama
• Beneficiário: Alexsandra Conceição Apolinário
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado