Hydrogel Formulation Containing PLGA Nanoparticles for Controlled Codelivery of Vitamin D and Chlorhexidine as a Promising Approach for Postdental Implant Applications

Abstract Tooth loss can have a significant impact on oral health and quality of life, and dental implants are currently the standard option for its replacement. However, implant failure still occurs, with bacterial infection and inadequate osseointegration being the most common causes. In this context, vitamin D3 was selected for its known pro-osteogenic role, while chlorhexidine (CHX), a widely used antiseptic with recognized bactericidal and bacteriostatic activity, was chosen as the antimicrobial component. To enable controlled and localized delivery of both molecules, two types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed, CHX- and vitamin D3-loaded NPs. The produced NPs displayed an average size of 140 nm, a polydispersity index below 0.2, and negative ζ-potentials. Encapsulation efficiency reached 39% for CHX and 98% for vitamin D3, and transmission electron microscopy confirmed their spherical morphology. In vitro release assays demonstrated an initial burst release followed by a slower release phase for 3 days under simulated physiological conditions, while stability tests under storage conditions showed preservation of the nanoformulations’ physicochemical properties for at least 2 months. Antibacterial assays against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) confirmed the antimicrobial effect of CHX-loaded NPs. Cytotoxicity studies in human dermal fibroblasts indicated that combining both formulations (50 nM vitamin D3 and 0.01% w/v CHX) was safe. To facilitate application in the oral cavity, the NP mixture was incorporated into a nontoxic, pseudoplastic hydrogel. These findings highlight the potential of this nanohydrogel as a localized therapeutic approach capable of providing localized antimicrobial activity and supporting conditions favorable to osseointegration, paving the way for improved long-term implant outcomes.