Polyethylene oxide-poloxamer 407 in situ forming gels: A dual drug delivery system for periodontal application

Abstract

Periodontitis is a complex disorder characterized by infection and inflammation that requires prolonged localized antibacterial and anti-inflammatory treatment. In situ forming gel (ISFG) drug delivery systems offer a promising approach for localized periodontal drug delivery. Poloxamer 407 (P407) is a well-reported thermosensitive polymer for ISFG systems; however, enhancement of the gel strength to withstand in vivo stress is challenging. Herein, we utilized polyethylene oxide (PEO) to increase the mechanical strength of poloxamer 407 (P407)-based in situ gels, particularly for periodontal delivery of antibacterial and antioxidant/anti-inflammatory drugs. Two formulations were developed: one containing the hydrophilic drug metronidazole (MTD) and the other with curcumin-loaded zein nanoparticles (CZ). The prepared systems were assessed for syringeability, gel hardness, adhesiveness, mucoadhesiveness, and drug release. Furthermore, cytocompatibility with human dermal fibroblasts, antibacterial efficacy, and anti-inflammatory activities were also evaluated to establish their role in periodontitis. The addition of PEO significantly enhanced gel hardness and adhesiveness, and the syringeability force (but within an acceptable limit of 40 N); however, PEO did not affect the release of MTD. PEO did not compromise the cytocompatibility or antibacterial properties of the formulations. CZ-loaded gels also exhibited antioxidant and antiinflammatory activities. The P407 system with curcumin nanoparticles showed aggregation during storage, whereas the PEO-P407 system maintained stable syringeability and nanoparticle dispersion. In conclusion, these findings indicate that PEO can improve both the mechanical properties and stability of nanoparticles-loaded P407-based gels for dual-drug delivery.