Gemcitabine sustained release to intratumoral click-crosslinked hyaluronic hydrogel for improved cancer therapy
- 주제(키워드) Hyaluronic acid , Anticancer , Click cross-linked
- 주제(DDC) 547
- 발행기관 아주대학교 일반대학원
- 지도교수 Moon Suk Kim
- 발행년도 2026
- 학위수여년월 2026. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000035334
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Melanoma remains a lethal skin cancer with high metastatic potential and limited tumor drug exposure under conventional systemic chemotherapy. Gemcitabine (Gem) has clinical value, but its efficacy in solid tumors is limited by a short half- life and dose-limiting toxicity. To address these issues, we developed a tumor- targeting click-crosslinked hyaluronic acid reservoir to limit and prolong gemcitabine exposure in melanoma and evaluated it in the B16F10 model. Simultaneous injection of two solutions—gemcitabine-loaded HA containing trans- cyclooctene and gemcitabine-loaded HA containing tetrazine—via a dual syringe triggered a reverse-electron-demand Diels-Alder reaction, forming a cohesive hydrogel within seconds. The resulting GE-Cx-HA matrix exhibited rapid crosslinking, excellent injectability, and stable viscoelastic properties suitable for field deployment. In release studies, GE-Cx-HA maintained gemcitabine release for an extended period compared to the non-crosslinked control, while locally sustaining therapeutically significant concentrations and limiting dispersion into surrounding tissues. In B16F10 tumor-bearing mice, GE-Cx-HA administered as a single intratumoral dose more effectively inhibited tumor growth than the free gemcitabine comparison group. Histopathological analysis revealed that H&E staining showed a reduction in treatment-related surviving tumor areas, while CD31 immunostaining suggested a persistent decrease in microvasculature within treated lesions. This reservoir maintained structural integrity in vivo, supporting sustained local delivery without repeated administration, potentially reducing systemic exposure and off-target toxicity. These data highlight that GE-Cx-HA is a practical, syringe-administerable, promising topical therapy that combines biocompatible click chemistry with the biocompatibility of hyaluronic acid to achieve gelation and controlled intratumoral chemotherapy tailored to the needs of cutaneous melanoma.
more목차
1. Introduction 1
2. Experimental 4
2.1. Materials 4
2.2. Fabrication of Cx-HA and GE-Cx-HA hydrogel 5
2.3. Rheology Measurements of GE-Cx-HA Formulations 6
2.4. Assessment of the injectability of click-crosslinked HA hydrogels 7
2.5. In vitro drug-release study 8
2.6. In vitro anticancer efficacy 9
2.7. Animal Experiments 10
2.8. Histological analysis 11
2.9. Data processing and statistical evaluation 12
3. Results 14
3.1. Preparation and physicochemical analysis of injectable formulations 14
3.2. Assessment of Injectability in Click-Crosslinked HA Hydrogels 16
3.3. In Vitro Anticancer Activity 21
3.4. In Vivo therapeutic performance of GE single and GE-Cx-HA hydrogel 25
3.5. Histology studies 28
4. Conclusion 32
REFERENCES 33
List of Publications 36
ABSTRACT (IN KOREAN) 37
