| Preparation and invitro evaluation of gatifloxacin -carboxymethyl chitosan nanoparticlesObjective To investigate the preparation method and optimization technique of a nanoparticle delayed-action preparation used in eyes, gatifloxacin-carboxymethyl chitosan nanoparticles with chitosan nano- particles as a carrier and to study the drug-release characteristic of gatifloxacin-carboxymethyl chitosan nanoparticles invitro.Methods The carboxymethyl chitosan was used as a carrier to prepare gatifloxacin nanoparticles. Nanoparticle size was evaluated by laser particle size determinator. The high performance liquid chromatography (HPLC) was used to detect the drug-loading rate and entrapment rate of particles. And it was used to test the invitro release. Results The mean size of the gatifloxacin-carboxymethyl chitosan nanoparticles was 0.233±0.030μm(pre-freeze-dry) and 0.246±0.032μm (post-freeze-dry). The drug-loading rate was 29.14%and entrapment rate was 62.47%. The release behavior of particles was confirmed to be a zero model.Conclusion The gatifloxacin-carboxymethyl chitosan nanoparticles could be prepared simply by gatifloxacin and carboxymethyl chitosan in mild condition without any organic solvents. The nanoparticles had a good sustained-release function. The topical application study of nanoparticle should be made to check its efficiency.Study on topical application of gatifloxacin -carboxymethyl chitosan nanoparticles in rabbit eyesObjective To investigate the concentration and pharmacokinetics in rabbit's cornea and aqueous humor after topically using gatifloxacin- carboxymethyl chitosan nanoparticles eye drops.Methods Thirty-six New Zealand albino rabbits were divided into 2 groups. Gatifloxacin nanoparticles solution (experiment group) and gatifloxacin normal solution (control group) were dropped on conjunctival sac of rabbits respectively. Aqueous humor and ocular tissue were collected at 0.125h, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, and 24h after instillation. The ultrastructure of cornea was observed by using the transmission electronic microscopy. Ocular pharmacokinetic parameters of gatifloxacin were calculated by 3P87 software.Results Ocular pharmacokinetic parameters of gatifloxacin in aqueous humor: each Cmax were 2.96±0.15and 1.85±0.03μg/ml, each Tmax were 1.55±0.25 and 0.58±0.05h, each AUC0-T were 17.72±1.15 and 5.92±0.28h·μg-1·ml-1, MRT were5.21±0.27 and 2.37±0.06h; and in cornea: each Cmax were 22.59±0.68 and 14.18±0.48μg/ml, each Tmax were 1.60±0.09 and 0.54±0.02h, each AUC0-T were 189.30±14.60 and 43.32±2.86h·μg-1·ml-1, MRT were 6.32±0.15 and 2.33±0.04h. No obvious change of corneal ultrastructure was found under the transmission electronic microscopy.Conclusion The gatifloxacin nanoparticles delivery system could be sustained in rabbit ocular tissue for a long time, and could enhance biological availability.
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