title: Liposome incorporated ion sensitive in situ gels for opthalmic delivery of timolol maleate.
abstract: This study was aimed to design a liposomal based ion-sensitive in situ ophthalmic delivery system of timolol maleate (TM). The TM liposome was produced by the reverse evaporation technique coupled with pH-gradients method (REVPR), and then was incorporated into deacetylated gellan gum gels. The TM liposome was demonstrated to be a round and uniform shape in TEM pictures. Compared with the TM eye drops, the TM liposome produced a 1.93 folds increase in apparent permeability coefficients (Papp), resulting in a significant increase of the corneal penetration. The TM-loaded liposome incorporated ion sensitive in situ gels (TM L-ISG) showed longer retention time on corneal surface compared with the eye drops using gamma scintigraphy technology. Draize testing showed that TM L-ISG was non-irritant for ocular tissues. The biggest efficacy of TM L-ISG occurred 30 min after eye drops administration, and efficacy disappeared after 240min. Then, compared with the eye drops, the optimal TM L-ISG could quickly reduce the intraocular pressure and the effective time was significantly longer (P≤0.05). These results indicate that liposome incorporated ion sensitive in situ gels have a potential ability for the opthalmic delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Wenji
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: yangxg123@163.com.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: pppwwwsss@163.com.
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003315:Cornea / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D006863:Hydrogen-Ion Concentration; D007429:Intraocular Pressure / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D009883:Ophthalmic Solutions; D010539:Permeability; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors; D013999:Timolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D005782:Gels; D008081:Liposomes; D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial; C048288:gellan gum; D013999:Timolol
keywords: Deacetylated gellan gum; Liposomal-ion sensitivity in situ gel; Ocular drug delivery system; Pharmacodynamics; Timolol maleate