Solvent exchange-induced in situ forming gel (ISG) is currently an appealing dosage form for periodontitis treatment via localized injection into the periodontal pocket. This study aims to apply Eudragit L and Eudragit S as matrix components of ISG by using monopropylene glycol as a solvent for loading levofloxacin HCl for periodontitis treatment. The influence of Eudragit concentration was investigated in terms of apparent viscosity, rheological behavior, injectability, gel-forming behavior, and mechanical properties. Eudragit L-based formulation presented less viscosity, was easier to inject, and could form more gel than Eudragit S-based ISG. Levofloxacin HCl-loading diminished the viscosity of Eudragit L-based formulation but did not significantly change the gel formation ability. Higher polymer loading increased viscosity, force-work of injectability, and hardness. SEM photographs and µCT images revealed their scaffold formation, which had a denser topographic structure and less porosity attained owing to higher polymer loading and less in vitro degradation. By tracking with fluorescence dyes, the interface interaction study revealed crucial information such as solvent movement ability and matrix formation of ISG. They prolonged the drug release for 14 days with fickian drug diffusion kinetics and increased the release amount above the MIC against test microbes. The 1% levofloxacin HCl and 15% Eudragit L dissolved in monopropylene glycol (LLM15) was a promising ISG because of its appropriate viscosity (3674.54 ± 188.03 cP) with Newtonian flow, acceptable gel formation and injectability (21.08 ± 1.38 N), hardness (33.81 ± 2.3 N) and prolonged drug release with efficient antimicrobial activities against S. aureus (ATCC 6538, 6532, and 25923), methicillin-resistant S. aureus (MRSA) (S. aureus ATCC 4430), E. coli ATCC 8739, C. albicans ATCC 10231, P. gingivalis ATCC 33277, and A. actinomycetemcomitans ATCC 29522; thus, it is the potential ISG formulation for periodontitis treatment by localized periodontal pocket injection.

Solvent exchange-induced in situ forming gel (ISG) has emerged as a versatile drug delivery system, particularly for periodontal pocket applications. In this study, we developed lincomycin HCl-loaded ISGs using a 40% borneol-based matrix and N-methyl pyrrolidone (NMP) as a solvent. The physicochemical properties and antimicrobial activities of the ISGs were evaluated. The prepared ISGs exhibited low viscosity and reduced surface tension, allowing for easy injection and spreadability. Gel formation increased the contact angle on agarose gel, while higher lincomycin HCl content decreased water tolerance and facilitated phase separation. The drug-loading influenced solvent exchange and matrix formation, resulting in thinner and inhomogeneous borneol matrices with slower gel formation and lower gel hardness. The lincomycin HCl-loaded borneol-based ISGs demonstrated sustained drug release above the minimum inhibitory concentration (MIC) for 8 days, following Fickian diffusion and fitting well with Higuchi’s equation. These formulations exhibited dose-dependent inhibition of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 8739, and Prophyromonas gingivalis ATCC 33277, and the release of NMP effectively inhibited Candida albicans ATCC 10231. Overall, the 7.5% lincomycin HCl-loaded 40% borneol-based ISGs hold promise as localized drug delivery systems for periodontitis treatment.

Borneol has been successfully employed as a gelling agent for in situ forming gel (ISG). While 40% borneol can regulate drug release, there is interest in novel approaches to achieve extended drug release, particularly through the incorporation of hydrophobic substances. Herein, triacetin was selected as a hydrophobic additive solvent for doxycycline hyclate (Dox)-loaded 40% borneol-based ISGs in N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO), which were subsequently evaluated in terms of their physicochemical properties, gel formation morphology, water sensitivity, drug release, and antimicrobial activities. ISG density and viscosity gradually decreased with the triacetin proportion to a viscosity of <12 cPs and slightly influenced the surface tension (33.14–44.33 mN/m). The low expelled force values (1.59–2.39 N) indicated the convenience of injection. All of the prepared ISGs exhibited favorable wettability and plastic deformation. Higher gel firmness from ISG prepared using NMP as a solvent contributed to the ability of more efficient controlled drug release. High triacetin (25%)-loaded ISG retarded solvent diffusion and gel formation, but diminished gel firmness and water sensitivity. ISG containing 5% triacetin efficiently prolonged Dox release up to 10 days with Fickian diffusion and presented effective antimicrobial activities against periodontitis pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Therefore, the Dox-loaded 40% borneol-based ISG with 5% triacetin is a potential effective local ISG for periodontitis treatment.

This research investigates the gel formation behaviour and drug-controlling performance of doxycycline-loaded ibuprofen-based in-situ forming gels (DH-loaded IBU-based ISGs) for potential applications in periodontal treatment. The investigation begins by exploring the physical properties and gel formation behaviour of the ISGs, with a particular focus on determining their sustained release capabilities. To gain a deeper understanding of the molecular interactions and dynamics within the ISGs, molecular dynamic (MD) simulations are employed. The effects of adding IBU and DH on reducing surface tension and water tolerance properties, thus affecting molecular properties. The phase transformation phenomenon is observed around the interface, where droplets of ISGs move out to the water phase, leading to the precipitation of IBU around the interface. The optimization of drug release profiles ensures sustained local drug release over seven days, with a burst release observed on the first day. Interestingly, different organic solvents show varying abilities to control DH release, with dimethyl sulfoxide (DMSO) demonstrating superior control compared to N-Methyl-2-pyrrolidone (NMP). MD simulations using AMBER20 software provide valuable insights into the movement of individual molecules, as evidenced by root-mean-square deviation (RMSD) values. The addition of IBU to the system results in the retardation of IBU molecule movement, particularly evident in the DMSO series, with the diffusion constant value of DH reducing from 1.2452 to 0.3372 and in the NMP series from 0.3703 to 0.2245 after adding IBU. The RMSD values indicate a reduction in molecule fluctuation of DH, especially in the DMSO system, where it decreases from over 140 to 40 Å. Moreover, their radius of gyration is influenced by IBU, with the DMSO system showing lower values, suggesting an increase in molecular compactness. Notably, the DH-IBU configuration exhibits stable pairing through H-bonding, with a higher amount of H-bonding observed in the DMSO system, which is correlated with the drug retardation efficacy. These significant findings pave the way for the development of phase transformation mechanistic studies and offer new avenues for future design and optimization formulation in the ISG drug delivery systems field.