Formulation and evaluation of in situ forming PLA implant containing tinidazole for the treatment of periodontitis

Abstract

Periodontitis is caused by periodontopathic bacteria and antibacterial agents are placed in a periodontal pocket with the intention of enhancing the local effect. To maximize the therapeutic effects while reducing the adverse effects, tinidazole was delivered by in situ forming system. One approach for reducing burst release rate was to testify in situ forming effect. The effect of 0%-10% (w/w) polyethylene glycol 400 and 3% (w/w) glycerol on the tinidazole release from a poly(DL-lactide) (PLA) injectable implant was evaluated. The results showed that the in vitro initial burst release rate was decreased in the presence of poly(ethyleneglycol) PEG 400 and glycerol. A formulation containing 30% (w/w) PLA (M(w) 7300) dissolved in 62% (w/w) N-methyl-2-pyrrolidone, 5% (w/w) PEG 400, and 3%(w/w) glycerol with 5% (w/w) tinidazole was shown to be optimum. Twelve adult beagle dogs were used in the periodontitis model. The treatment group I, II, and positive control group was administrated with gel containing 5%(w/w) tinidazole, 2.5%(w/w) tinidazole, and periocline, respectively. Dog studies revealed that periocline and the developed formulation could significantly decrease symptoms of periodontitis, and they were better than gel containing 2.5% (w/w) tinidazole. The developed formulation could sustain the release of tinidazole for local delivery over 7 days. These findings suggested that the developed formulation was a viable alternative to conventional drug to cure periodontitis.

Local delivery of minocycline-loaded PEG-PLA nanoparticles for the enhanced treatment of periodontitis in dogs

“…3 In brief, 8 weeks after dental ligature, dogs were anesthetized by intravenous injection of pentobarbital sodium. Fifty microliters of either minocycline solution in N-methyl-2-pyrrolidone (NMP) (2%), MIN-NPs, or Periocline were injected into the periodontal pocket of each beagle dog by a disposable syringe with a 21-gauge needle.…”

“…1,2 Considerable research has focused on the etiology of human periodontal disease, 3 and it has been generally accepted that chronic periodontitis is induced by microorganisms. Periodontal pockets provide a moist, warm, nutritious, and anaerobic environment that profits microbial colonization and multiplication.…”

“…Further, the side effects are reduced significantly. 3 However, some issues still exist. The vehicles of fibers and strips must be removed after complete release of the drug by professionals, and the wound is not conducive to recovery.…”

“…16 The application of gels is more convenient than fibers and strips, but the issues are burst release and the rapid local drug clearance of antimicrobials. 3 Biodegradable nanoparticles (NPs) have been developed rapidly over the past few years since they have shown great potential in drug delivery. 17 NPs have more advantages than other new formulations and many of the already-mentioned problems can be avoided.…”

“…To evaluate periodontal status, the clinical periodontal parameters of plaque index (PI), gingival index (GI), periodontal pocket depth (PPD), clinical attachment level, and bleeding on probing were recorded. 3 …”