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

Abstract

Periodontitis is an infectious and inflammatory disease 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, its low mechanical strength limits its ability to withstand in vivo stress. 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 (metronidazole) and antioxidant/anti-inflammatory drugs (curcumin). First, two types of formulations were developed: one containing the hydrophilic drug metronidazole (MTD) and the other with hydrophobic curcumin-loaded zein nanoparticles (CZ) to evaluate the effect of PEO. The prepared systems were assessed for gelation time, gelation temperature, syringeability, gel hardness, adhesiveness, drug release, and degradation. The addition of PEO significantly enhanced gel hardness, adhesiveness, and the syringeability force (but within a reported acceptable limit of 40 N); however, PEO did not affect the release of MTD. The cytocompatibility of the formulations was not compromised by the presence of PEO. CZ-loaded gels also exhibited antioxidant and anti-inflammatory activities via DPPH scavenging assay and in LPS-polarized macrophages, respectively. The P407 system with curcumin nanoparticles showed a significant increase in syringeability force during storage, whereas the PEO-P407 system maintained stable syringeability over 2 months. Lastly, both drugs were incorporated into a single formulation with PEO, and their release profiles were comparable to those observed in formulations containing the individual drugs. This indicates that the combined formulation did not adversely affect the release of either drug nor influence the antibacterial activity. In conclusion, these findings indicate that PEO can improve both the mechanical properties of ISFG and stability of nanoparticles-loaded P407-based gels with the ability to deliver hydrophilic and hydrophobic drug-loaded nanoparticles.