In vivo characterization of a new type of biodegradable starch microsphere for transarterial embolization

Abstract

Transarterial embolization is an established minimally invasive treatment for solid tumors. Unintended inflammation, foreign body reactions and ischemia-triggered neoangiogenesis are clinical drawbacks of permanent embolic materials. The aim of the current study was to characterize a new type of biodegradable starch microsphere with regard to angiographic and histopathological features such as patterns of acute arterial occlusion as well as induction of tissue necrosis, microsphere biodegradation, and inflammation and foreign body reactions during follow-up. Key characteristics of both biodegradable prototypes (L1 and L2; prototype groups) were as follows: microspheres are biodegradable by serum α-amylase, produced from chemically crosslinked potato starch to different extents, in a diameter range of ∼300-800 µm, differing in size distribution and featuring a microsphere deformation of ∼1%. In vivo transarterial embolization with L1 and L2, while applying clinical standard techniques, was performed and compared with clinically established permanent microspheres (Embosphere®500-700 and Embosphere®700-900; control groups). Twenty-four pig kidneys were embolized with the different embolic materials by following the study protocol, and there were no technical failures or complications. Parenchymal necrosis with interstitial calcification was observed in all kidneys independent of the type of embolic material used. Compared with the permanent embolic materials, biodegradable microspheres showed complete (L1) or partial (L2) biodegradation within one week after transarterial embolization, and induced a comparable (L1) or a lower (L2) degree of arterial wall necrosis and a lower degree of inflammation and foreign body reactions. In conclusion, the presented new type of biodegradable microsphere is promising, and could be further evaluated in terms of clinical translation.

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

“…There are many kinds of carrier polymers for biodegradable microspheres, including both natural biodegradable polymers and synthetic ones. Most of the natural polymers come from plants, animals or microorganisms, such as starch (Lin et al, 2013 ; Sommer et al, 2018 ; Tesfay et al, 2020 ), chitosan (Li et al, 2017 ; Calzoni et al, 2019 ; Huang et al, 2019 ; Li et al, 2020 ; Cirri et al, 2021 ), alginate (Campana et al, 2020 ; Ghumman et al, 2020 ; Panchal & Vasava, 2020 ), gelatin (Kim et al, 2018 ; Chen et al, 2019 ; Javanbakht et al, 2019 ), etc. They are used as microsphere carriers due to their rich properties and good biocompatibility (Prajapati et al, 2015 ).…”

Embolic Materials: Understanding the Ocean of Choices

“…For example, Sommer et al demonstrated reduced post-procedure complications when using a novel biodegradable microsphere in comparison with established permanent microspheres. 37 Another theoretical advantage of particle resorption is minimizing the risk of long-term immune reactions. Similarly, the development of visible particles has been an active area of research with several studies reporting computed tomography (CT) and magnetic resonance imaging (MRI) visible particles.…”

Recent advances and applications of microspheres and nanoparticles in transarterial chemoembolization for hepatocellular carcinoma

“…To address the issues of postoperational ischemia and angiogenesis, biodegradable microspheres were developed which are either synthetic or extracted from natural sources (Mao et al, 2012). Natural biodegradable microspheres include starch microspheres (Gross & Albrecht, 2020; Orlacchio et al, 2020; Sommer et al, 2018; Yamasaki et al, 2012), silk fibroin (SF)/elastin (Figure 3) (Chen et al, 2020; Poursaid et al, 2015; Poursaid, Jensen, Nourbakhsh, et al, 2016), gelatin microspheres (Katsumori et al, 2017; Sakuhara et al, 2019), alginate (Xuan et al, 2017; Zeng et al, 2018), carrageenan (Liu et al, 2020), and Bletilla striata (Luo et al, 2019).…”

“…New microspheres were produced from chemically crosslinked potato starch to different extents, in a diameter range of 300–800 μm, differing in size distribution and featuring a microsphere deformation of about 1%. The starch microspheres can be biodegradable by serum α‐amylase within 54–72 h which is much longer than the degradation time (90 min) of EmboCept® S (Sommer et al, 2018).…”