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.

Localized intra-periodontal pocket drug delivery using an injectable in situ forming gel is an effective periodontitis treatment. The aqueous insoluble property of rosin is suitable for preparing a solvent exchange-induced in situ forming gel. This study aims to investigate the role of incorporating lime peel oil (LO) on the physicochemical properties of injectable in situ forming gels based on rosin loaded with 5% w/w doxycycline hyclate (DH) in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP). Their gel formation, viscosity, injectability, mechanical properties, wettability, drug release, and antimicrobial activities were evaluated. The presence of LO slowed gel formation due to the loose precipitate formation of gel with a high LO content. The viscosity and injectability were slightly increased with higher LO content for the DH-loaded rosin-based in situ forming gel. The addition of 10% LO lowered gel hardness with higher adhesion. LO incorporation promoted a higher drug release pattern than the no oil-added formulation over 10 days and the gel formation rate related to burst drug release. The drug release kinetics followed the non-Fickian diffusion mechanism for oil-added formulations. LO exhibited high antimicrobial activity against Porphyromonas gingivalis and Staphylococcus aureus. The DH-loaded rosin in situ forming gel with an addition of LO (0, 2.5, 5, and 10% w/w) inhibited all tested microorganisms. Adding 10% LO to rosin-based in situ forming gel improved the antimicrobial activities, especially for the P. gingivalis and S. aureus. As a result, the study demonstrates the possibility of using an LO amount of less than 10% loading into a rosin-based in situ forming gel for efficient periodontitis treatment.

Fluconazole (FZ) is a potential antifungal compound for treating superficial and systemic candidiasis. However, the use of conventional oral drug products has some limitations. The development of buccal film may be a potential alternative to oral formulations for FZ delivery. The present study involved the development of novel FZ-loaded solid lipid nanoparticles (FZ-SLNs) in pectin solutions and the investigation of their particle characteristics. The particle sizes of the obtained FZ-SLNs were in the nanoscale range. To produce pectin films with FZ-SLNs, four formulations were selected based on the small particle size of FZ-SLNs and their suitable polydispersity index. The mean particle sizes of all chosen FZ-SLNs formulations did not exceed 131.7 nm, and the mean polydispersity index of each formulation was less than 0.5. The properties of films containing FZ-SLNs were then assessed. The preparation of all FZ-SLN-loaded pectin films provided the mucoadhesive matrices. The evaluation of mechanical properties unveiled the influence of particle size variation in FZ-SLNs on the integrity of the film. The Fourier-transform infrared spectra indicated that hydrogen bonds could potentially form between the pectin-based matrix and the constituents of FZ-SLNs. The differential scanning calorimetry thermogram of each pectin film with FZ-SLNs revealed that the formulation was thermally stable and behaved in a solid state at 37 °C. According to a drug release study, a sustained drug release pattern with a burst in the initial stage for all films may be advantageous for reducing the lag period of drug release. All prepared films with FZ-SLNs provided a sustained release of FZ over 6 h. The films containing FZ-SLNs with a small particle size provided good permeability across the porcine mucosa. All film samples demonstrated antifungal properties. These results suggest the potential utility of pectin films incorporating FZ-SLNs for buccal administration.

Localized delivery systems have been typically designed to enhance drug concentration at a target site and minimize systemic drug toxicity. A rosin/cinnamon oil (CO) in situ forming gel (ISG) was developed for the sustainable delivery of imatinib mesylate (IM) against colorectal cancer cells. CO has been claimed to express a potent anticancer effect against various cancer cells, as well as a synergistic effect with IM on colorectal cancer cells; however, poor aqueous solubility limits its application. The effect of rosin with the adding CO was assessed on physicochemical properties and in vitro drug release from developed IM-loaded rosin/CO-based ISG. Moreover, in vitro cytotoxicity tests were conducted against two colorectal cancer cells. All formulations exhibited Newtonian flow behavior with viscosity less than 266.9 cP with easier injectability. The adding of CO decreased the hardness and increased the adhesive force of the obtained rosin gel. The gel formation increased over time under microscopic observation. CO-added ISG had a particle-like gel appearance, and it promoted a higher release of IM over a period of 28 days. All tested ISG formulations revealed cytotoxicity against HCT-116 and HT-29 cell lines at different incubation times. Thus, CO-loaded rosin-based ISG can act as a potentially sustainable IM delivery system for chemotherapy against colorectal cancer cells.

The aim of this study was to prepare and characterize the imatinib mesylate (IM)-loaded gamboge-based ISG system for local administration of an anticancer agent against colorectal carcinoma. The ISG formulations were prepared in dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP). The physicochemical properties, drug release profile, and cytotoxicity of the developed formulations were assessed. The developed ISG demonstrated Newtonian flow behavior with acceptable rheological and mechanical properties. The viscosity of the developed ISG, measured at less than 80 cP, and the applied forces of less than 50 N·mm, indicated easy administration using clinical injection techniques. Upon contact with an aqueous phase, the ISG immediately formed a porous cross-sectional structure, enabling sustained release of IM over 14 days. The release profile of IM was fitted to the quasi-Fickian diffusion mechanism, and the release rate could be controlled by the types of solvent and the amount of IM content. The developed IM-loaded gamboge ISG effectively inhibited colorectal cancer cells, including HCT116 and HT29 cell lines, with less than 20% cell viability observed at a concentration of 1% w/w IM after 2 days of incubation. This suggests that the developed ISG may potentially serve as an injectable system for localized anticancer delivery against colorectal cells, potentially reducing the side effects of systemic chemotherapy and improving patient adherence.