title: Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight chitosan for the treatment of glaucoma: vitro and vivo study.
abstract: The aims of this study were to design and characterize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLN) with and without modification of low molecular weight chitosan (CS) and compare their potentials for ocular drug delivery. Low molecular weight CS was obtained via a modified chemical oxidative degradation method. SLN with CS (CS-SLN-MTZ) and without CS (SLN-MTZ) were prepared according to a modified emulsion-solvent evaporation method. SLN-MTZ and CS-SLN-MTZ were 199.4 ± 2.8 nm and 252.8 ± 4.0 nm in particle size, -21.3 ± 1.9 mV and +31.3 ± 1.7 mV in zeta potential, respectively. Physical stability studies demonstrated that CS-SLN-MTZ remained stable for at least 4 months at 4 °C, while SLN-MTZ no more than 2 months. A prolonged in vitro release profile of MTZ from CS-SLN-MTZ was obtained compared with SLN-MTZ. Furthermore, CS-SLN-MTZ presented a better permeation property in excised rabbit cornea. In vivo studies indicated that the intraocular pressure lowering effect of CS-SLN-MTZ (245.75 ± 18.31 mmHg × h) was significantly better than both SLN-MTZ (126.74 ± 17.73 mmHg × h) and commercial product Brinzolamide Eye Drops AZOPT® (171.17 ± 16.45 mmHg × h). The maximum percentage decrease in IOP of CS-SLN-MTZ (42.78 ± 7.71%) was higher than SLN-MTZ (27.82 ± 4.15%) and was comparable to AZOPT (38.06 ± 1.25%). CS-SLN-MTZ showed no sign of ocular irritancy according to the Draize method and the histological examination.
authors.affiliation: School of Pharmacy, Nanjing Medical University , Nanjing, Jiangsu , China .
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Sunmin
authors.initials: S
authors.lastname: Jiang
authors.forename: Kun
authors.initials: K
authors.lastname: Shi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry; D003315:Cornea / Q000378:metabolism; D004311:Double-Blind Method; D004337:Drug Carriers; D004355:Drug Stability; D005260:Female; D005901:Glaucoma / Q000188:drug therapy*; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008297:Male; D008704:Methazolamide / Q000008:administration & dosage* / Q000494:pharmacology*; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011817:Rabbits
chemical_list: D004337:Drug Carriers; D008055:Lipids; D048271:Chitosan; D008704:Methazolamide
keywords: Intraocular pressure-lowing effect; low molecular weight chitosan; methazolamide; ocular irritancy; solid lipid nanoparticle