Biocompatibility Evaluation of a Dexamethasone Mucoadhesive Nanosystem: Preclinical and Preliminary Clinical...

There is a strong need for drug delivery systems that are both highly compatible with biological tissues and effective when used in the oral mucosa. While gels, creams, or ointments are currently employed for this purpose, their oral bioavailability is constrained by the limited contact time with mucosal tissue.

In response to this challenge, we developed and evaluated the efficacy of a multilayer mucoadhesive system incorporated with Dexamethasone Sodium Phosphate (DEX-P) for oral mucosal delivery. An electrospun multilayer system was created and subjected to biocompatibility and efficacy testing via in vitro and ex vivo approaches, finally culminating in an acceptability trial in healthy human volunteers. The multilayer system was created using Poly-Vinyl Pyrrolidone (PVP) and Poly ε-Caprolactone (PCL) as a polymeric base and Polycarbophil (NOVEON® AA-1, PCF) serving as an adhesion enhancer to facilitate the unidirectional release of Dexamethasone Sodium Phosphate (DEX-P).

The nanofibers matrices underwent morphological characterization by Scanning Electron Microscopy (SEM), and DEX-P release was evaluated using ex vivo porcine mucosa, yielding promising results. In vitro cytotoxicity was evaluated through the MTT assay, employing HFF-1 cells. The cell viability ranged from 78 to 96%, suggesting the safety of the polymers used. The tested dose range of DEX on cell lines did not decrease below 75%, indicating its safety in terms of in vivo cytotoxicity. Biocompatibility was evaluated on animal models, without significant tissue damage observed.

The results of this study demonstrate the potential of the developed multilayer mucoadhesive system as an effective platform for oral mucosal drug delivery. The combination of PVP and PCL provides a stable and tunable matrix for drug incorporation, while PCF successfully enhances mucoadhesion and controlled drug release. The electrospun architecture enables precise drug loading and unidirectional release, which is crucial for minimizing systemic absorption and maximizing local therapeutic effects. The high cell viability observed in vitro and the absence of significant tissue damage in vivo underline the biocompatibility of the system. Moreover, the positive feedback from human volunteers not only indicates functional efficacy but also practical usability, which is essential for clinical translation. Taken together, these findings support the feasibility of using this multilayer nanofiber system as a safe and effective vehicle for oral mucosal therapy, particularly for localized delivery of corticosteroids, such as DEX-P.

Human in vivo studies demonstrated prolonged adhesion and a favorable perception of the system.