Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15

Tamara Krajnović,Ludger Wessjohann,Dijana Drača,Goran Kaluđerović,Sanja Mijatović,Danijela Maksimović-Ivanić,David Edeler,Katharina Wolf

doi:10.3390/nano8050322

Tamara Krajnović, Ludger Wessjohann + Show 6 more

Open Access

https://doi.org/10.3390/nano8050322

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Abstract

In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1–SBA-15|EO5: 8–36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.

Highlights

Quinones represent a large family of compounds having diverse biological properties
SBA-15 is prepared by a standard sol-gel procedure and afterwards calcined [38]
Preparation and characterization of mesoporous silica SBA-15 loaded with various quantities of EO (→ SBA-15|EO1–SBA-15|EO5: 8–36%) is presented

Summary

Introduction

Quinones represent a large family of compounds having diverse biological properties. Emodin (EO; 1,3,8-trihydroxy-6-methylanthraquinone) belongs to a group of molecules with an anthraquinone core, isolated from the roots and barks of many plants, molds, and lichens [1,2]. Its multiple biological activities can be ascribed to its affinity to modulate different enzymes, and to intercalate in DNA leading to the inhibition of the action of topoisomerase II [3]. Inhibition of PTK signaling pathways by EO will reflect on the cellular response to different growth factors, cytokines, or hormones [7]. Emodin inhibited HER-2/neu tyrosine kinase activity, suppressed growth and induced differentiation of HER-2/neu-overexpressing breast cancer cells in vitro and in vivo [13]. It is well described that EO is able to induce apoptotic cell death in numerous cancer cell lines: tongue squamous, cervical, pancreatic, breast, colon, leukemia, lung, and hepatocellular cells [2,6,8,9,10,11,12]. EO is able to sensitize tumor cells to some chemotherapeutics (e.g., cisplatinol (abiplastin), doxorubicin (adriablastin), 5-FU, arsenic trioxide, gemcitabine) [2,20,21]

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