title: Chitosan grafted methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanosuspension for ocular delivery of hydrophobic diclofenac.
abstract: This study aimed to develop a cationic nanosuspension of chitosan (CS) and methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) for ocular delivery of diclofenac (DIC). MPEG-PCL-CS block polymer was synthesized by covalent coupling of MPEG-PCL with CS. The critical micelle concentration of the MPEG-PCL-CS block polymer was 0.000692 g/L. DIC/MPEG-PCL-CS nanosuspension (mean particle size = 105 nm, zeta potential = 8 mV) was prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The nanosuspension was very stable without apparent physical property changes after storage at 4 °C or 25 °C for 20 days, but it was unstable in the aqueous humor solution after 24 h incubation. Sustained release of the encapsulated DIC from the nanosuspension occurred over 8 h. Neither a blank MPEG-PCL-CS nanosuspension nor a 0.1% (mass fraction) DIC/MPEG-PCL-CS nanosuspension caused ocular irritation after 24 h of instillation. Enhanced penetration and retention in corneal tissue was achieved with a Nile red/MPEG-PCL-CS nanosuspension compared with a Nile red aqueous solution. In vivo pharmacokinetics studies showed enhanced pre-corneal retention and penetration of the DIC/MPEG-PCL-CS nanosuspension, which resulted in a higher concentration of DIC (Cmax) in the aqueous humor and better bioavailability compared with commercial DIC eye drops (P < 0.01).
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shi
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Zichao
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Renlong
authors.initials: R
authors.lastname: Liang
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology &Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004008:Diclofenac / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005128:Eye Diseases / Q000188:drug therapy*; D006801:Humans; D008297:Male; D051379:Mice; D009883:Ophthalmic Solutions / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits
chemical_list: D004337:Drug Carriers; D009883:Ophthalmic Solutions; D011091:Polyesters; D004008:Diclofenac; C016240:polycaprolactone; D011092:Polyethylene Glycols; D048271:Chitosan; C000595209:polyethylene glycol 1000