盐酸左氧氟沙星眼用纳米粒温敏凝胶的制备及体外释放考察
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摘要
目的制备盐酸左氧氟沙星眼用纳米粒温敏凝胶,考察其体外释药行为。方法采用离子交联法制备眼用盐酸左氧氟沙星壳聚糖纳米粒,以泊洛沙姆407和188为温敏基质,以人工泪液稀释前后的胶凝温度为评价指标,采用二因素五水平的中心复合设计-响应曲面法优选温敏凝胶处方,释放度检测法考察该处方的体外释药性。结果载药纳米粒的平均粒径为(60.7±5.1)nm,包封率为(62.5±1.8)%,载药量为(10.43±0.30)%;最佳温敏凝胶基质组成为泊洛沙姆407∶泊洛沙姆188(22%∶6%),胶凝温度为(32.3±0.2)℃,载药纳米粒温敏凝胶24h释放总量达71.9%。结论盐酸左氧氟沙星纳米粒温敏凝胶结合纳米粒和原位凝胶的优点,具有理想的胶凝温度和缓释效果,有望成为眼部给药新剂型。
Objective To prepare ocular levofloxacin hydrochloride nanoparticles thermo-sensitive in situ gels(LVFX-NPs-TISG)and to study its drug release in vitro. Methods Ocular levofloxacin hydrochloride nanoparticles were prepared by ionic cross-linking method. Poloxamer 407 and 188 were used as the thermo-sensitive material. A central composite design-response surface method(CCD-RSM)was adopted to optimize formulation of gel by measuring gelation temperatures with and without artificial tears. A release method was used to study the drug release in vitro. Results The mean diameter of drug loaded nanoparticles was(60.7±5.1)nm. The encapsulation efficiency and drug loading were(62.5±1.8)% and(10.43±0.30)%. The optimized formula was selected as poloxamer 407∶poloxamer188(22%∶6%)and the gelation temperature was(32.3±0.2)℃. Within 24 hours,accumulative release of levofloxacin hydrochloride was 71.9%. Conclusions LVFX-NPs-TISG showed the advantages of nanoparticles and in situ gels with the properties of desired gelation temperature and sustained drug release in vitro,which hopefully provides a promising ophthalmic drug delivery of levofloxacin hydrochloride.
Objective To prepare ocular levofloxacin hydrochloride nanoparticles thermo-sensitive in situ gels(LVFX-NPs-TISG)and to study its drug release in vitro. Methods Ocular levofloxacin hydrochloride nanoparticles were prepared by ionic cross-linking method. Poloxamer 407 and 188 were used as the thermo-sensitive material. A central composite design-response surface method(CCD-RSM)was adopted to optimize formulation of gel by measuring gelation temperatures with and without artificial tears. A release method was used to study the drug release in vitro. Results The mean diameter of drug loaded nanoparticles was(60.7±5.1)nm. The encapsulation efficiency and drug loading were(62.5±1.8)% and(10.43±0.30)%. The optimized formula was selected as poloxamer 407∶poloxamer188(22%∶6%)and the gelation temperature was(32.3±0.2)℃. Within 24 hours,accumulative release of levofloxacin hydrochloride was 71.9%. Conclusions LVFX-NPs-TISG showed the advantages of nanoparticles and in situ gels with the properties of desired gelation temperature and sustained drug release in vitro,which hopefully provides a promising ophthalmic drug delivery of levofloxacin hydrochloride.
引文
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[10]李颖,汤湛,王俏.眼用原位凝胶研究进展[J].中国药学杂志,2015,50(14):1174-1179.
[11]Katiyar S,Pandit J,Mondal R S,et al.In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma[J].Carbohydrate Polymers,2014,102(1):117-124.
[12]Ur-rehman T,Tavelin S,Grobner G.Chitosan in situ gelation for improved drug loading and retention in poloxamer 407gels[J].Int J Pharm,2011,409(1-2):19-29.
[13]何为,薛卫东,唐斌.优化试验设计方法及数据分析[M].北京:化学工业出版社,2016:218.
[14]谢元彪,岳鹏飞,但济修,等.纳米制剂体外释放度评价方法的研究进展[J].中国药学杂志,2016,51(6):861-866.
[15]李颖,汤湛,尹丽娜,等.苄达赖氨酸温敏型眼用原位凝胶的体外释放性及角膜渗透性考察[J].中国现代应用药学,2016,33(5):580-586.
[16]田芳,王玉柱,杨凯,等.尼非韦罗阴道温敏原位凝胶的流变学研究[J].中国新药杂志,2013,22(3):345-350.
[2]Koch H R,Kulus S C,Roessler M,et al.Corneal penetration of fluoroquinolones:aqueous humor concentrations after topical application of levofloxacin 0.5%and ofloxacin 0.3%eyedrops[J].J Cataract Refract Surg,2005,31(7):1377-1385.
[3]赵平.左氧氟沙星外用制剂的研究及临床应用[J].世界最新医学信息文摘,2013,13(16):195-197.
[4]毛如虎.胶粒系统用于眼用制剂的研究进展[J].中国药业,2013,22(13):102-104.
[5]李莎莎,孙朋超,黄维维,等.眼部给药研究新进展[J].中国医药工业杂志,2015,46(1):97-102.
[6]Chen D,Sun K,Mu H,et al.pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric delivery system[J].Int J Nanomedicine,2012,7:2621-2630.
[7]Klouda L,Mikos A G.Thermoresponsive hydrogels in biomedical applications[J].Eur J Pharm Biopharm,2008,68(1):34-45.
[8]Hao J,Wang X,Bi Y,et al.Fabrication of a composite system combining solid lipid nanoparticles and thermosensitive hydrogel for chanllenging ophthalmic drug delivery[J].Colloids Surf B Biointerfaces,2013,114(8):111-120.
[9]国家药典委员会.中华人民共和国药典[M].四部.北京:中国医药科技出版社,2015,通则0931:121.
[10]李颖,汤湛,王俏.眼用原位凝胶研究进展[J].中国药学杂志,2015,50(14):1174-1179.
[11]Katiyar S,Pandit J,Mondal R S,et al.In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma[J].Carbohydrate Polymers,2014,102(1):117-124.
[12]Ur-rehman T,Tavelin S,Grobner G.Chitosan in situ gelation for improved drug loading and retention in poloxamer 407gels[J].Int J Pharm,2011,409(1-2):19-29.
[13]何为,薛卫东,唐斌.优化试验设计方法及数据分析[M].北京:化学工业出版社,2016:218.
[14]谢元彪,岳鹏飞,但济修,等.纳米制剂体外释放度评价方法的研究进展[J].中国药学杂志,2016,51(6):861-866.
[15]李颖,汤湛,尹丽娜,等.苄达赖氨酸温敏型眼用原位凝胶的体外释放性及角膜渗透性考察[J].中国现代应用药学,2016,33(5):580-586.
[16]田芳,王玉柱,杨凯,等.尼非韦罗阴道温敏原位凝胶的流变学研究[J].中国新药杂志,2013,22(3):345-350.