Solubility-Enhanced dragon's blood in a PEI/PAA xerogel powder for accelerated chronic wound healing.

Chronic refractory wounds present a significant global healthcare challenge, characterized by persistent inflammation and impaired tissue repair that conventional dressings often fail to adequately modulate. While Dragon's blood (Dra), a traditional Chinese medicine, offers potent anti-inflammatory and angiogenic properties highly suitable for this complex microenvironment, its clinical translation is severely hindered by inherent hydrophobicity and low bioavailability. To address these limitations and bridge the therapeutic gap, we developed a novel Dra-loaded polyethyleneimine/polyacrylic acid (PEI/PAA) xerogel powder. We first optimized the solubility of Dragon's blood extract (Dra-Ext) using solid dispersion and inclusion complex technologies. Comparative analysis indicated that solid dispersion with PVPK30 achieved superior solubility enhancement (12.12 μg/mL, a 46-fold increase) compared to the HP-β-CD inclusion complex. The optimized xerogel powder (Dra-SD/PEI/PAA powder) exhibited rapid gelation (<30 s), high fluid absorption (340.5% ± 10% within 30 s), excellent self-healing capabilities, and sustained drug release (85.8% ± 0.3% over 48 h at pH 7.4). Furthermore, the dressing demonstrated superior hemostatic activity (coagulation time = 0.85 ± 0.07 min) and favorable biocompatibility. In a rat model of chronic refractory wounds, the Dra-SD/PEI/PAA treatment significantly accelerated wound closure (99.50% healing rate at day 14), promoted collagen deposition, and downregulated pro-inflammatory cytokines (IL-1β by 61.25% and IL-6 by 84.85%). These findings indicate that the Dra-SD/PEI/PAA platform effectively integrates solubility enhancement with rapid hemostasis and inflammation modulation, offering a promising therapeutic strategy for chronic wound management.