Synthesis, characterization and evaluation of tinidazole-loaded mPEG-PDLLA (10/90) in situ gel forming system for periodontitis treatment.
Traditional in situ gel forming systems are potential applications for parenteral administration but always accompanied with burst release. To overcome this limitation, the tinidazole (TNZ)-loaded in situ gel forming system using a diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(d,l-lactide) (mPEG-PDLLA), was designed. The formulation of the mPEG-PDLLA-based TNZ in situ gel forming system contained 5% (w/w) TNZ, 0.4% glycerol, 5 ml N-methyl pyrrolidone (NMP) and 35% (w/w) mPEG-PDLLA. The in situ gel forming system showed sustained TNZ release over 192 h with low burst effect (around 7% in the first 8 h) in the in vitro release study. Additionally, in vivo studies were performed on rabbits with ligature-induced periodontitis, and the concentration of TNZ in the gingival crevicular fluid (GCF) as well as the pharmacokinetic parameters was calculated and the pharmacological effect of TNZ-loaded in situ gel forming (mPEG-PDLLA)-based system was found effective. Finally, histological studies revealed that the gel was a safe formulation with low irritation. The desirable drug release kinetics combined with the excellent in vivo characteristics highlight the potential of the gel in the treatment of periodontitis. Therefore, these results confirmed that the TNZ-loaded in situ gel forming mPEG-PDLLA-based system could reduce burst release of TNZ and act as a sustained-release and injectable drug depot for periodontitis treatment.
a State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University , Nanjing , China and.
Yu
Y
Tian
a State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University , Nanjing , China and.
Yan
Y
Shen
b China State Institute of Pharmaceutical Industry , Shanghai , China.
Minli
M
Jv
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D005782:Gels / Q000737:chemistry*; D005883:Gingival Crevicular Fluid / Q000378:metabolism; D010518:Periodontitis / Q000188:drug therapy*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D014011:Tinidazole / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D011091:Polyesters; D011108:Polymers; D014011:Tinidazole; D011092:Polyethylene Glycols; C033616:poly(lactide)
Burst release periodontitis; in situ gel forming system; mPEG–PDLLA; tinidazole