Academic Journal
Intratumoral Injectable Click-Crosslinked Hyaluronic Acid Depot for Sustained Gemcitabine Delivery.
| Τίτλος: | Intratumoral Injectable Click-Crosslinked Hyaluronic Acid Depot for Sustained Gemcitabine Delivery. |
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| Συγγραφείς: | Son KE; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea., Lee Y; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea., Kim Y; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea., Lee S; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea., Kim Y; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea., Kang TW; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea., Kim K; Department of Biomedical Engineering, Jungwon University, 85 Munmu-ro, Goesan-Eup, , Goesan-Gun, Chuncheongbuk-do, 28023, Republic of Korea. kyungsook.kim@jwu.ac.kr., Kim MS; Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea. moonskim@ajou.ac.kr.; Research Institute, Medipolymers, Woncheon Dong, 332-2, Suwon, 16522, Korea. moonskim@ajou.ac.kr. |
| Πηγή: | Tissue engineering and regenerative medicine [Tissue Eng Regen Med] 2026 Aug; Vol. 23 (6), pp. 815-831. Date of Electronic Publication: 2026 Jun 12. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer International Publishing co-published with Korean Tissue Engineering and Regenerative Medicine Country of Publication: Korea (South) NLM ID: 101699923 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2212-5469 (Electronic) Linking ISSN: 17382696 NLM ISO Abbreviation: Tissue Eng Regen Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Seoul : Springer International Publishing co-published with Korean Tissue Engineering and Regenerative Medicine, [2012]- |
| Ιατρικοί όροι (MeSH): | Deoxycytidine*/analogs & derivatives , Deoxycytidine*/pharmacology , Deoxycytidine*/chemistry , Deoxycytidine*/pharmacokinetics , Hyaluronic Acid*/chemistry , Hyaluronic Acid*/pharmacology , Cross-Linking Reagents*/chemistry , Melanoma, Experimental*/drug therapy , Melanoma, Experimental*/pathology , Melanoma, Experimental*/metabolism , Click Chemistry* , Drug Delivery Systems*, Hydrogels/chemistry ; Delayed-Action Preparations/pharmacology ; Gemcitabine ; Animals ; Mice ; Cell Line, Tumor ; Mice, Inbred C57BL ; Injections, Intralesional ; Female |
| Περίληψη: | Background: Gemcitabine (GE) is a widely used chemotherapeutic agent for solid tumors; however, its therapeutic efficacy is often compromised by rapid diffusion from the tumor site and insufficient intratumoral retention following local administration. Injectable hydrogel-based drug depots offer a promising strategy to prolong local drug availability and enhance antitumor efficacy while minimizing systemic toxicity. Methods: An intratumoral injectable, gemcitabine-loaded, click-crosslinked hyaluronic acid hydrogel (GE + Cx-HA) was developed using a bioorthogonal click reaction to enable rapid in situ gelation. Physicochemical properties, gelation behavior, viscoelasticity, and injectability through a fine-gauge needle were characterized. In vitro gemcitabine release profiles and anticancer activity against B16F10 melanoma cells were evaluated. Antitumor efficacy, angiogenesis inhibition, and systemic toxicity were assessed in a murine melanoma model following a single intratumoral injection. Results: GE + Cx-HA remained in a low-viscosity solution state prior to injection and rapidly formed a stable hydrogel depot upon click crosslinking without needle clogging. The crosslinked network significantly suppressed burst release and enabled sustained gemcitabine release in vitro. Compared with free gemcitabine, GE + Cx-HA exhibited prolonged anticancer activity against B16F10 melanoma cells. In vivo, a single intratumoral administration of GE + Cx-HA markedly inhibited tumor growth and angiogenesis for up to 18 days, without observable systemic toxicity. Conclusion: These results demonstrate that GE + Cx-HA functions as an effective intratumoral drug depot, providing sustained local chemotherapy and enhanced antitumor efficacy, highlighting its potential as a localized therapeutic platform for solid tumor treatment. (© 2026. Korean Tissue Engineering and Regenerative Medicine Society.) |
| Competing Interests: | Declarations. Conflict of interest: The authors declare no competing financial interests. Ethical approval: All animal procedures were conducted in accordance with protocols reviewed and approved by the Institutional Animal Care and Use Committee of Ajou University College of Medicine (IACUC approval number: 2024–0030). In vivo experiments were performed in compliance with the guidelines of the Ajou University Medical Center for the care and use of laboratory animals and adhered to internationally accepted standards for animal welfare. |
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| Grant Information: | RS-2025-25417684 National Research Foundation of Korea |
| Contributed Indexing: | Keywords: Click-crosslinked hyaluronic acid hydrogel; Gemcitabine; Intratumoral drug delivery; Tumor suppression |
| Substance Nomenclature: | 0 (Gemcitabine) 0W860991D6 (Deoxycytidine) 9004-61-9 (Hyaluronic Acid) 0 (Cross-Linking Reagents) 0 (Hydrogels) 0 (Delayed-Action Preparations) |
| Entry Date(s): | Date Created: 20260612 Date Completed: 20260729 Latest Revision: 20260731 |
| Update Code: | 20260731 |
| PubMed Central ID: | PMC13415715 |
| DOI: | 10.1007/s13770-026-00819-z |
| PMID: | 42283951 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2212-5469 |
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| DOI: | 10.1007/s13770-026-00819-z |