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

白桦酸 体内 卵巢癌 光动力疗法 卵巢癌 化学 微粒 体外 光敏剂 癌症研究 药理学 癌症 医学 生物 生物化学 内科学 生物技术 遗传学 天体生物学 有机化学
作者
Alessandra Freitas Serain,Lavinia Morosi,Tommaso Ceruti,Cristina Matteo,Marina Meroni,Elaine Minatel,Massimo Zucchetti,Marcos José Salvador
出处
期刊:Journal of Photochemistry and Photobiology B-biology [Elsevier]
卷期号:224: 112328-112328 被引量:2
标识
DOI:10.1016/j.jphotobiol.2021.112328
摘要

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-β-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 (λ = 420 nm) under different conditions (2.75 J/cm2, 5.5 J/cm2, and 11 J/cm2) 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.
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