n-phenacylthiazolium-bromide and Periodontitis

This study aimed to develop pH-responsive polylactide-glycolic acid co-polymer and chitosan (PLGA/chitosan) nanosphere as an inflammation-responsive vehicle and evaluate the potential of the nanosphere encapsulating metronidazole, an antibiotic, and N-phenacylthiazolium bromide (PTB), a host modulator, for treating periodontitis.. PLGA/chitosan nanospheres were fabricated using oil-in-water emulsion method. Experimental periodontitis was induced on the rat maxillae, and the sites were randomly allocated to four treatment categories, including periodontitis alone (PR), periodontitis with nanospheres alone, nanospheres encapsulating metronidazole (MT) and nanospheres encapsulating PTB (PB). The ligature was retained until the animals were killed, and the treatment outcome was evaluated by the progression of periodontal bone loss (PPBL), inflammatory cell infiltration and collagen deposition.. The encapsulated drug was released rapidly from the nanospheres without significant initial burst release at pH 5.5. Compared with group PR, PPBL was significantly reduced in groups MT and PB on day 4 (P<.05). On day 21, PPBL was significantly lower in group PB (P<.05). In groups MT and PB, inflammation was significantly reduced in groups MT and PB relative to groups PR and periodontitis with nanospheres alone (P<.05), and collagen deposition was significantly greater relative to group PR (P<.05).. PLGA/chitosan nanospheres encapsulating metronidazole or PTB showed potential for modulating periodontitis progression.

Topics: Animals; Anti-Infective Agents; Chitosan; Disease Models, Animal; Disease Progression; Lactic Acid; Metronidazole; Nanospheres; Periodontitis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Thiazoles

Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan-based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix.. A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature-induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density.. PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal.. Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis.

Topics: Alveolar Bone Loss; Animals; Hydrogel, Polyethylene Glycol Dimethacrylate; Periodontitis; Rats; Rats, Sprague-Dawley; Thiazoles

Advanced glycation end products (AGEs) are involved in the inflammatory process and are considered to be etiologic factors of diabetic periodontitis. The purpose of this study is to investigate the capability of N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker, in the modulation of periodontitis in various disease phases.. Mitogenesis and cytotoxicity of human periodontal ligament cells (hPDLCs) undergoing PTB treatment were evaluated in vitro. In vivo biomodulation was investigated by systemically administering PTB in the induction, progression, and recovery phases of ligature-induced periodontitis in rats, with the results evaluated by microcomputed tomography, histology, immunohistochemistry of the AGE and AGE receptor (RAGE), and gene expression of tumor necrosis factor-α (TNF-α), RAGE, periostin, fibronectin, and type I collagen.. Significantly promoted mitogenesis and reduced cytotoxicity of hPDLCs were noted with 0.05 to 0.1 mM PTB treatment at 24 hours. Systemic PTB administration significantly reduced periodontal bone loss, AGE deposition, and expressions of TNF-α and RAGE but elevated the periostin level in all three phases of periodontitis.. PTB inhibits the induction and progression of periodontitis and facilitates its recovery via improving cellular viability and inhibiting the AGE-RAGE axis.

Topics: Alveolar Bone Loss; Animals; Blood Glucose; Cell Adhesion Molecules; Cell Culture Techniques; Cell Line; Cell Survival; Collagen Type I; Disease Models, Animal; Disease Progression; Fibronectins; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Immunohistochemistry; Male; Periodontal Ligament; Periodontitis; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Thiazoles; Tumor Necrosis Factor-alpha