Alginate-pectin nanocomposite powders embedding PLGA nanoparticles for in situ hydrogel formation: A tuneable platform for drug delivery to wound.

Nanotechnology-based systems represent promising tools for wound healing, although the direct use of nanoparticle suspensions remains limited by poor handling and clinical applicability. In this work, we developed an innovative delivery strategy based on nanoparticles-in-microparticles (NiMs), where PLGA nanoparticles were incorporated into alginate-pectin microparticles through a continuous process combining prilling and spray drying. NiMs were prepared with increasing nanoparticle loadings (5%, 20%, and 50% w/w) and betamethasone used only as a model drug. All formulations showed good encapsulation efficiency (60%) and underwent rapid gelation upon contact with simulated wound fluid, forming hydrogels with tuneable viscoelastic properties. Moreover, SEM and thermal analyses confirmed the physical entrapment of nanoparticles and NP content enhances the strength of in situ gels. This is beneficial for maintaining the integrity of dressings under mechanical stress and ensuring that gels remain in place in the wound bed. In vitro drug release followed a biphasic profile with an initial burst phase (up to 80% drug within 1-3 h) followed by sustained release over 24 h, consistent with therapeutic needs for wound management. The results obtained demonstrate that NiMs are a versatile platform combining ease of administration, in situ gel formation, and controlled drug release, thus holding strong potential as next generation wound dressings.