The effect of RGD-targeted and non-targeted liposomal Galbanic acid on the therapeutic efficacy of pegylated liposomal doxorubicin: From liposomal preparation to in-vivo studies

[Display omitted] The anti-cancer therapeutic application of Galbanic acid (Gba) as a strong antiangiogenic sesquiterpene coumarin has been limited due to its low water solubility. This issue necessitates developing new liposomal formulations for the efficient delivery of Gba in vivo. In this study,...

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Published in:International journal of pharmaceutics 2021-07, Vol.604, p.120710-120710, Article 120710
Main Authors: Nik, Maryam Ebrahimi, Jaafari, Mahmoud Reza, Mashreghi, Mohammad, Nikoofal-Sahlabadi, Sara, Amin, Mohamadreza, Sadeghnia, Hamid Reza, Iranshahi, Mehrdad, Navashenaq, Jamshid Gholizadeh, Malaekeh-Nikouei, Bizhan
Format: Article
Language:English
Subjects:
Angiogenesis
Cancer
Doxorubicin
Galbanic acid
Liposomes
RGD peptide
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Summary:[Display omitted] The anti-cancer therapeutic application of Galbanic acid (Gba) as a strong antiangiogenic sesquiterpene coumarin has been limited due to its low water solubility. This issue necessitates developing new liposomal formulations for the efficient delivery of Gba in vivo. In this study, various liposomal formulations were prepared by a thin-film hydration method, and Gba was incorporated into the liposomal bilayers, which consequently increased its release profile compared to formulations in our previous study prepared by remote loading methods. The most stable formulation with desired properties was selected and decorated with RGD peptide (cyclo [Arg-Gly-Asp-D-Tyr-Cys]) to target tumor vasculature actively. The fluorescently-labeled model liposomes showed that the targeting could improve the receptor-mediated endocytosis of the liposomes higher than those prepared in our previous study in vitro in human umbilical vein endothelial cells (HUVECs), which was confirmed by chicken chorioallantoic membrane angiogenesis (CAM) model in vivo. Although not significant, it also could increase the accumulation of liposomes in colon tumors. In BALB/c mice bearing colon cancer, not only non-targeted Gba liposomes but also even RGD-targeted ones combinatorial therapy with pegylated liposomal doxorubicin could improve the anti-tumor efficacy as compared to their monotherapy. These outcomes have strong consequences for cancer therapy.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2021.120710