Layered double hydroxide-nanoengineered injectable hydrogel based on oxidised pectin/carboxymethyl chitosan for...

Deep vein thrombosis prophylaxis with enoxaparin (ENO) requires frequent subcutaneous injections, posing treatment burden and compliance challenges. However, the sustained delivery of ENO remains challenging due to its highly anionic nature and rapid diffusion from conventional delivery matrices. Here, we developed an injectable hydrogel incorporating ENO-loaded layered double hydroxide (LDH) nanocarriers within an oxidised pectin/carboxymethyl chitosan (OP/CMCs) matrix to enable prolonged release. The hydrogel forms via Schiff base chemistry, yielding rapid gelation (∼7 min), self-healing properties, and strong tissue adhesion suitable for minimally invasive administration. The LDH nanocarriers provided dual-mechanism retention through electrostatic interactions and tortuous diffusion pathways. The optimised formulation containing 6.0 wt% CMCs and 0.1 wt% OP with a 1:0.5 LDH:ENO mass ratio demonstrated minimal burst release (∼5.3% at day 1) and sustained delivery over 13 days with ∼40.1% cumulative release. In vitro, in ovo, and in vivo studies confirmed good biocompatibility and stable subcutaneous depot formation. Crucially, the prolonged thrombin time demonstrated the capability to regulate blood coagulation. Consequently, the sustained-release ENO hydrogel system exhibited the potential to significantly reduce injection frequency compared to standard regimens, thereby improving patient compliance and quality of life.