 The healing process of chronic wounds remains a major clinical challenge exacerbated by the risk of microbial infection and bacterial resistance to common antibiotics. In this study, non-antibiotic nanohybrid formulations combining chlorhexadine dihydrochloride, CHX, and clay minerals were developed to improve wound healing in chronic lesions. Two different methods were used to prepare the nanohybrids, intercalation in solution, and spray drying. The nanohybrids were characterized using solid state techniques and computational calculations to assess their interactions with clays at the molecular level. Biocompatibility and antimicrobial activity tests were conducted to evaluate the biocompatibility and potential microbicidal effects of the nanomaterials. The results showed that the nanohybrids exhibited good biocompatibility and microbicidal effects, especially when prepared via spray drying. This suggests that the greater contact area of the spray dried nanohybrids with target cells and bacteria may contribute to their enhanced microbicidal effectiveness. This article was authored by Catarina Valentino, Tomas Martinez Rodriguez, Ana Borrego Sanchez, and others. We are article.tv, links in the description below.