Evaluation of polyelectrolyte nanoparticles of chitosan and hyaluronic acid as topical delivery systems for cytotoxic agents

Autor(es)

Hirokawa, Camila M. ; Passos, Julia S. ; Nunes, Jessica R. ; Lopes, Luciana B.

• Tipo de documento: Artigo Científico
• Fonte: COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS; v. 702, p. 15-pg., 2024-08-10.

Resumo

In this study, we developed polyelectrolyte complexes (PECs), composed of hyaluronic acid and chitosan, aiming at obtaining a bioadhesive topical formulation for potential application for skin cancer treatment. Selected nanocarriers were obtained at a 1:1 (w/w) ratio of polyelectrolytes (0.25 mg/mL each) and probe sonication, displayed nanometric size (209.4 nm, PDI = 0.19), and cationic zeta potential (+28.0 +28.0 mV). PECs presented bioadhesive potential, demonstrated by shifts in size and zeta potential upon incubation with mucin, and reduced transepidermal water loss. Paclitaxel (PTX) and 5-fluorouracil (5-FU), cytotoxic drugs with distinct physical- chemical characteristics, were incorporated at 0.25 and 0.75 %, respectively; propylene glycol addition was necessary for PTX incorporation. Compared to the control, 2.3- (9.4 +/- 3.6 +/- 3.6 mu g/cm2) 2 ) and 4.5-fold (2.8 +/- 0.8 +/- 0.8 mu g/cm2) 2 ) increases in PTX penetration into the stratum corneum and viable skin layers, respectively, were observed after 12 hours. No increase in 5-FU penetration was demonstrated. Incorporation in PECs resulted in slight increases in the cytotoxicity of PTX and 5-FU against melanoma cells, reducing IC50 50 values by 1.5- and 1.2-fold (1.55 and 35.10 mu M for PTX and 5-FU, respectively) compared to the control solutions. IC50 50 values found for keratinocytes were higher (5.74 and 162.6 mu M for paclitaxel and 5-FU, respectively). At non-cytotoxic concentrations, drug loaded PECs promoted 24-31 % reductions on cell migration, suggesting that drug incorporation in PECs did not hinder their biological effects. (AU)

• Processo FAPESP: 21/06755-0 - Avaliação de nanoemulsões para administração tópico-transdérmica de fenretinida como estratégia de quimioprevenção
• Beneficiário: Jessica Ribeiro Nunes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• 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: 21/12658-7 - Desenvolvimento de nanopartículas de polieletrólitos de quitosana e ácido hialurônico para administração intraductal
• Beneficiário: Camila Megumi Hirokawa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 20/01208-8 - Sistemas nanoestruturados bioadesivos para administração intraductal e tratamento localizado do Câncer de Mama
• Beneficiário: Julia Sapienza Passos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto