Hydroxyethyl Starch

To report the results of the randomized (2:1) pivotal study evaluating the safety and effectiveness of the Instylla Embrace Hydrogel Embolic System (HES), consisting of 2 low-viscosity, liquid precursors that form a biocompatible crosslinked polyethylene glycol hydrogel, compared with standard of care (SOC) in the embolization of hypervascular tumors (HVTs).

This prospective, multicenter, randomized, noninferiority study of adults with malignant and benign HVT had dual primary endpoints of safety and effectiveness. Safety was freedom of major adverse events (MAEs) through 30 days including death, nontarget embolization, unintended tissue ischemia, pulmonary embolism, vascular injury requiring intervention, renal or hepatic failure, abscess in target organ, or toxic/allergic reaction to HES. Effectiveness (technical success) was delivery of the embolic agent to the tumor feeding vessel(s), with stasis of flow assessed by an independent blinded imaging core laboratory. Additional endpoints were assessed through 180 days. Adverse events and imaging were independently adjudicated.

There were 150 subjects (56% men and 44% women), with mean age of 65.4 years (SD ± 12.9) and tumors of ≤ 8 cm, recruited from 22 international centers. HES-treated subjects (102) had 118 tumors and 148 vessels treated, and SOC-treated subjects (48) had 56 tumors and 72 vessels treated. Both primary endpoints were successfully achieved. Freedom from MAE was 99% (P < .001), and technical success was achieved in 88.6% of HES and 77.9% of SOC (P = .001).

This randomized study of a peripheral liquid embolic demonstrated that the Instylla Embrace HES met its primary endpoints in the treatment of HVTs.

Myocardial infarction (MI) induces pathological remodeling that drives heart failure. Dual-targeted approaches addressing myocardial repair and angiogenesis are crucial for improving post-infarct prognosis. Previous research has demonstrated that hesperadin (Hes), a CaMKII inhibitor, exhibits anti-apoptotic activity, while vascular endothelial growth factor (VEGF) enhances angiogenesis following infarction. Although these two drugs may hold potential for combination therapy, their co-delivery is compromised by opposing physicochemical properties: Hes is highly hydrophobic, whereas VEGF is hydrophilic and can cause significant adverse effects when administered systemically. Here, we report a supramolecular hydrogel (SHV gel) constructed from hyaluronic acid (HA) and cucurbit[7]uril (CB[7]) to enable synchronized and sustained co-delivery of Hes and VEGF. CB[7] encapsulates Hes through host-guest recognition, thereby enhancing drug dispersibility and loading, while HA confines VEGF to preserve its bioactivity and prolong its release. In vitro and in vivo data reveal that SHV hydrogels combine favorable biocompatibility with sustained co-release of Hes and VEGF, showing superior synergistic efficacy against MI through anti-apoptosis, promoting angiogenesis, inhibiting myocardial remodeling and improving cardiac function compared to mono-component hydrogels. This supramolecular platform represents a promising multifunctional therapeutic strategy for precise MI intervention and clinical translation. STATEMENT OF SIGNIFICANCE: Myocardial infarction (MI) often progresses to heart failure because injured heart muscle dies and blood supply remains insufficient. Combining anti-apoptotic and pro-angiogenic therapies could improve recovery, but co-delivering a hydrophobic small molecule and a fragile, hydrophilic protein in one formulation is difficult, and systemic administration of vascular endothelial growth factor (VEGF) can cause adverse side effects. Here, we develop an injectable supramolecular hydrogel (SHV gel) built from hyaluronic acid and cucurbit[7]uril to synchronize delivery of hesperadin and VEGF. Cucurbit[7]uril encapsulates hesperadin to enhance solubility and loading, while the hyaluronic acid network confines VEGF to preserve bioactivity and prolong release. The resulting hydrogel shows good biocompatibility and synergistically reduces cardiomyocyte apoptosis, promotes angiogenesis, limits remodeling, and improves cardiac function in MI models.