Polymeric material plays an important role as a matrix former in the modulation of drug release of antimicrobial-loaded in situ forming gel (ISG) for efficient periodontitis treatment. This study was conducted to compare three polymers, namely bleached shellac (BS), Ethocel (EC) and Eudragit RS (ERS), as matrix formers of doxycycline hyclate (DH)-loaded solvent exchange-induced ISG. All prepared ISGs, except 25% EC ISG, exhibited the Newtonian flow behaviour. Transformation from solution into matrix-like was achieved rapidly within 5 min. Increasing the amount of these polymers extended the release of DH. DH-loaded EC and ERS ISG systems exhibited high antimicrobial activity, and all ISGs were effective in inhibiting the growth of Staphylococcus aureus , Escherichia coli , Streptococcus mutans , Porphyromonas gingivalis and Candida albicans . By comparison, the DH-loaded ERS ISG, through the solvent exchange mechanism, was found to be ease in injection with low viscosity and sustained the release with higher concentration, meanwhile, it also exhibited interesting in vitro degradability and antimicrobial activities. Therefore, the DH-loaded ERS ISG exhibited a potential use for localized periodontal drug delivery system for the treatment periodontitis.

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Modulation with the suppression of infection and inflammation is essential to the successful treatment of periodontitis. An aqueous insoluble hydrophobic anti-inflammatory compound, i.e., ibuprofen (IBU), was investigated in this study as the matrix-forming agent of a doxycycline hyclate (DH)-loaded solvent removal-induced in situ forming gel (ISG) using dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) as the solvents. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, injectability, mechanical properties, gel formation, and drug release, were determined. Their antimicrobial activities were tested using agar cup diffusion, and their anti-inflammatory activity was assessed using thermal inhibition of protein denaturation of egg albumin. Increasing the IBU content decreased the density, pH, surface tension, and contact angle but increased the viscosity, force and work of injection, and gel formation of IBU-based ISG solution. Although their water tolerance values decreased with the increase in IBU content, the addition of DH and the use of NMP led to high water tolerance. The characterization of the dried gel remnants of ISGs presented no change in IBU crystallinity and thermal properties and confirmed no chemical interaction among the components of ISGs. The obtained transformed IBU matrix prolonged the release of DH and IBU from ISGs over 7 days from its tortuously packed IBU matrix with small pores, and conformed well with Fickian diffusion mechanism. The developed DH-loaded solvent removal-induced IBU-based ISGs exhibited efficient antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Candida albicans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. IBU in formulation promoted the antimicrobial activity of ISGs, whereas DH and NMP promoted the anti-inflammatory activity of ISGs. Consequently, the DH-loaded solvent removal-induced IBU-based ISGs proposed in this study show great potential as an effective bioactive drug delivery system for periodontitis treatment by localized periodontal pocket injection.

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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.