ArticleTissue engineering and regenerative medicine2026
Intratumoral Injectable Click-Crosslinked Hyaluronic Acid Depot for Sustained Gemcitabine Delivery.
Article in Tissue engineering and regenerative medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGemcitabine (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.
methodsAn 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.
resultsGE + 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.
conclusionThese 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.
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