Development of a novel biodegradable chemo-radioembolic formulation for transarterial treatment of hepatocellular carcinoma
A Talk by Asseel Alregib
School of Medicine, Taylor’s University, Subang Jaya, Malaysia
About this talk
Asseel Hisham Alregib1, Yin How Wong1, Azahari Kasbollah2, Eng Hwa Wong1, Chai Hong Yeong1
1 School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, 47500 Subang Jaya, Selangor, Malaysia 2 Medical Technology Division, Malaysian Nuclear Agency, 43000 Bangi, Selangor, Malaysia
Abstract: Hepatocellular carcinoma (HCC) is the 5th common cancer in men and 7th in women worldwide. HCC has a high mortality and short survival rates as most patients are diagnosed at the intermediate or advanced stage. Chemoembolization and radioembolization have been established as promising treatments for locally advanced solid tumours. The treatments aim to achieve synergistic anti-tumour effects from the combination of chemotherapy, radiation therapy and embolization. However, chemoembolization and radioembolization are administered as two separate treatments. This study ought to develop a novel biodegradable microspheres formulation containing both radioactive samarium-153 (Sm-153) and Doxorubicin (Dox) for Transarterial chemo-radioembolization of advanced HCC.
Polyhydroxybutyrate-co-3-hydroxyvalerate (PHBV) microspheres loaded with the radionuclide Samarium-153 (Sm-153) and chemotherapy drug doxorubicin (DOX) were synthesized by solvent evaporation. Different physicochemical properties such as particle size, microspheres morphology, thermal stability, Sm-153 radioactivity and Dox content were evaluated in this study. The in-vitro release of DOX from the microspheres was conducted in phosphate buffered saline at 37°C.
The developed Sm-153 and DOX-loaded PHBV (Sm-Dox-PHBV) microspheres shown a smooth and spherical morphology with a mean diameter of 33±1.05 m. Both Sm-153 (12.80±0.01%) and Dox (66.00±0.12%) were successfully incorporated into the PHBV microsphere. The formulation achieved a nominal radioactivity of 4.20 ± 0.16 GBq per gram and the concentration of Dox was 1.89±0.36 mg per gram of microspheres. The microspheres remained stable when heated up to 150C. The in-vitro release of DOX from the Sm-Dox-PHBV microspheres achieved a cumulative release of 41.5 ± 0.15% at 430 hours.
In this study, a novel biodegradable chemo-radioembolic microspheres formulation loaded with Sm-153 and Dox was successfully developed to deliver both radioactive and chemotherapeutic agents for transarterial treatment of HCC. The Sm-153 emits both therapeutic beta and diagnostic gamma radiations for post-procedural microspheres distribution monitoring, while Dox is a validated anti-tumour drug. The microspheres demonstrated suitable physiochemical properties as a chemo-radioembolic agent. Further studies are needed to evaluate the therapeutic efficiency of the developed microspheres through cell line and animal studies.
Describe funding body that supported the work (if any)
The study is funded by the Fundamental Research Grant Scheme (FRGS/1/2019/SKK06/TAYLOR/02/3) of the Ministry of Higher Education, Malaysia.
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