Betulinic acid and its spray dried microparticle formulation: In vitro PDT effect against ovarian carcinoma cell line and in vivo plasma and tumor disposition

Autor(es)

Serain, Alessandra F. ^[1] ; Morosi, Lavinia ^[2] ; Ceruti, Tommaso ^[2] ; Matteo, Cristina ^[2] ; Meroni, Marina ^[2] ; Minatel, Elaine ^[3] ; Zucchetti, Massimo ^[2] ; Salvador, Marcos J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biol Vegetal, PPG BTPB, Cidade Univ Zeferino Vaz, Campinas, SP - Brazil

^[2] Ist Ric Farmacol Mario Negri IRCCS, Dept Oncol, Lab Canc Pharmacol, Via Mario Negri 2, I-20156 Milan - Italy

^[3] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biol Estrutural & Func, Cidade Univ Zeferino Vaz, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY; v. 224, NOV 2021.
• Citações Web of Science: 0

Resumo

The race against ovarian cancer continue to motivate the research worldwide. It is known that many antitumor drugs have limited penetration into solid tumor tissues due to its microenvironment, thus contributing to their low efficacy. Therapeutic modalities have been exploited to elicit antitumor effects based on microenvironment of tumor, including Photodynamic therapy (PDT). Prospection of natural small molecules and nanotechnology are important tools in the development of new ways of obtaining photoactive compounds that are biocompatible. The Betulinic acid (BA) has shown potential biological effect as bioactive drug, but it has low water solubility. Thus, in the present study, owing to the poor solubility of the BA, its free form (BAF) was compared to a spray dried microparticle betulinic acid/HP-beta-CD formulation (BAC) aiming to assess the BAF and BAC efficacy as a photosensitizer in PDT for application in ovarian cancer. BAF and BAC were submitted to assays in the presence of LED (lambda = 420 nm) under different conditions (2.75 J/cm(2), 5.5 J/cm(2), and 11 J/cm(2)) and in absence of irradiation, after 5 min or 4 h of contact with ovarian carcinoma cells (A2780) or fibroblast murine cells (3T3). Furthermore, HPLC-MS/MS and MALDI-MSI methods were developed and validated in plasma and tumor of mice proving suitable for in vivo studies. The results found a greater photoinduced cytotoxic effect for the BAC at low concentration for A2780 when irradiated with LED with similar results for fluorescence microscopy. The results motivate us to continue the studies with the BA as a potential antitumor bioactive compound. (AU)

• Processo FAPESP: 14/26320-4 - Estudo químico de Sinningia (Gesneriaceae) e avaliação do efeito biológico fotoinduzido para aplicação em PDT
• Beneficiário: Alessandra Freitas Serain
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/03726-8 - Estudo químico e biológico integrado para a busca de substâncias bioativas em espécies vegetais* e desenvolvimento de procedimentos analíticos. *(Amaranthaceae, Gesneriaceae, Myrtaceae e Annonaceae)
• Beneficiário: Marcos José Salvador
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/19523-4 - Espectrometria de massas por imagem para estudo de distribuição de fármacos em diferentes tecidos tumorais
• Beneficiário: Alessandra Freitas Serain
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 16/06407-3 - Estudo químico e biotecnológico de Sinningia (Gesneriaceae) e avaliação do efeito biológico fotoinduzido para aplicação em PDT
• Beneficiário: Alessandra Freitas Serain
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto