title: Bioadhesive chitosan-loaded liposomes: A more efficient and higher permeable ocular delivery platform for timolol maleate.
abstract: The aim of this study was to develop and characterize a novel colloidal system, namely, timolol maleate chitosan coated liposomes (TM-CHL) to enhance the ocular permeation, precorneal residence time and bioavailability. The resulting TM-CHL was the most promising formulation with a mean particle size of 150.7nm and an EE% of 75.83±1.61%. In vitro release of the TM-CHL showed an extended drug release profile. The TM-CHL exhibited significant mucin adhesion and compared with commercial eye drops, TM-CHL produced a 3.18-fold increase in the apparent permeability coefficient (Papp), resulting in a significant enhancement of corneal permeation. In addition, the gamma scintigraphic study and the pharmacokinetic study showed that TM-CHL could be retained at the corneal surface for longer time compared with eye drops. The ocular irritation study indicated that the developed liposomes produced no significant irritant effects. Furthermore, pharmacodynamics results showed that the maximum intraocular pressure(IOP) produced by TM-CHL was (19.67±1.14) mmHg compared with the (23.80±1.49) mmHg for TM eye drops, revealing that TM-CHL was more effective in reducing the IOP. These results demonstrate that CHL is a potentially useful carrier for ocular drug delivery, which could improve the efficacy of TM.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Yu
authors.affiliation: College of Pharmacy, Liaoning University, Shenyang 110036, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
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: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yuan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: yangxg123@163.com.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: pppwwwsss@163.com.
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D065546:Drug Liberation; D007429:Intraocular Pressure / Q000187:drug effects; D008081:Liposomes; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy; D010316:Particle Size; D010539:Permeability; D011817:Rabbits; D013999:Timolol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000959:Antihypertensive Agents; D008081:Liposomes; D013999:Timolol; D048271:Chitosan
keywords: Bioadhesive; Chitosan; Gamma scintigraphic; Liposomes; Ocular drug delivery; Pharmacodynamics