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PP-64

Gelatin-derived hydrogel with natural anthracycline derivative epirubicin

for combination therapy in brain tumor

2,3
1
4
Chia-Yu Hsu, Hung-Wei Yang, Hung-Chun Wang, Chiung‐Yin Huang, Kuo‐Chen
5,6
,1
Wei, 5,6,7 Pin-Yuan Chen, Hao-Han Pang*
5,6

1 Center for Drug Research and Development, Collage of Human Ecology, Chang Gung
University of Science and Technology, Taoyuan, Taiwan.
2 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
3 Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
4 Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung,
Taiwan.
5 Neuroscience Research Center, Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan.
6 Department of Neurosurgery, New Taipei Municipal TuCheng Hospital, Taoyuan, Taiwan.
7 Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
* E-mail: hhpang@mail.cgust.edu.tw

Abstract
Glioblastoma (GBM) is a highly fatal tumor of the central nervous system with a poor
prognosis. The median survival after surgery plus chemoradiation is ~14.6 months, and rapid
postoperative recurrence remains common. Current local delivery approaches deliver drugs too
rapidly and have limited effect against tumor cells. To overcome this drawback, we developed
a blue light–crosslinking hydrogel that gels rapidly in situ and adheres tightly to tissue, enabling
controlled chemotherapy, radiotherapy, and enhanced laser interstitial thermal therapy (LITT)
to suppress residual disease. We aimed to: i) define factors governing efficient encapsulation of
chemotherapeutics and radiosensitizers within the hydrogel; ii) demonstrate gelation
performance, LITT enhancement, and in vitro drug-release kinetics; and iii) evaluate antitumor
efficacy in vivo tumor models. Building on these objectives, we employed gelatin, a natural
collagen-derived biopolymer, as the scaffold for its biocompatibility and tissue affinity; while
epirubicin, a clinically used anthracycline and derivative of the natural product doxorubicin,
was co-encapsulated with Cisplatin to enable synergistic local therapy. This platform is versatile,
as the hydrogel system can encapsulate not only chemotherapeutics but also other natural-
product–derived agents for potential combination treatments. This multi-treatment system
effectively prevented recurrence and prolonged the median survival of GBM-bearing mice. The
combination of a natural-polymer matrix with anthracycline, delivered by rapid blue-light
gelation and retained via strong tissue adhesion, supports a practical platform for local,
postoperative control of GBM. Our findings highlight the value of integrating naturally derived
components into photo-crosslinking hydrogels for the prevention of brain tumor recurrence.

Keywords: Glioblastoma; Hydrogel; Gelatin; Epirubicin; Photothermal therapy