title: Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: preparation, characterization, and in vivo evaluation.
abstract: The purpose of this study was to evaluate the feasibility of in situ thermosensitive hydrogel based on chitosan in combination with disodium α-d-Glucose 1-phosphate (DGP) for ocular drug delivery system. Aqueous solution of chitosan/DGP underwent sol-gel transition as temperature increased which was flowing sol at room temperature and then turned into non-flowing hydrogel at physiological temperature. The properties of gels were characterized regarding gelation time, gelation temperature, and morphology. The sol-to-gel phase transition behaviors were affected by the concentrations of chitosan, DGP and the model drug levocetirizine dihydrochloride (LD). The developed hydrogel presented a characteristic of a rapid release at the initial period followed by a sustained release and remarkably enhanced the cornea penetration of LD. The results of ocular irritation demonstrated the excellent ocular tolerance of the hydrogel. The ocular residence time for the hydrogel was significantly prolonged compared with eye drops. The drug-loaded hydrogel produced more effective anti-allergic conjunctivitis effects compared with LD aqueous solution. These results showed that the chitosan/DGP thermosensitive hydrogel could be used as an ideal ocular drug delivery system in terms of the suitable sol-gel transition temperature, mild pH environment in the hydrogel as well as the organic solvent free.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Chen
authors.forename: Xinru
authors.initials: X
authors.lastname: Li
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yating
authors.initials: Y
authors.lastname: Fan
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017332:Cetirizine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048271:Chitosan / Q000737:chemistry*; D003233:Conjunctivitis, Allergic / Q000188:drug therapy*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D005958:Glucosephosphates / Q000737:chemistry*; D006168:Guinea Pigs; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008297:Male; D044367:Phase Transition; D011817:Rabbits; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D005958:Glucosephosphates; D039563:Histamine H1 Antagonists, Non-Sedating; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C472067:levocetirizine; D048271:Chitosan; C031590:glucose-1-phosphate; D017332:Cetirizine